€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****DEV ONCOL***** Stirpe F Barbieri L RIBOSOME-INACTIVATING PROTEINS AS POSSIBLE CHEMOTHERAPEUTIC AGENTS In: Dev Oncol (1984) 15:142-6 Ribosome-inactivating proteins (RIP) have been identified in many plants and may be present in all plants. They damage 80S (eukaryotic) ribosomes, thereby inhibiting protein synthesis. In mol wt (the 12 RIP thus far characterized have a mol wt of about 30,000), specific inhibition of ribosomal protein synthesis in cell-free systems, and toxicity to mice, rats, or intact cells, RIP resemble the A-chains of ricin, abrin, modeccin, and Viscum album (mistletoe) toxin. The proteins appear to be enzymatic (catalytic) and do not require cofactors for activity. The absence of a B-chain may explain the comparatively small effects of RIP on intact cells, although cellular sensitivities to their actions vary greatly from one cell type to another. These A-chain-like proteins may be substituted for A-chains in preparing conjugates with suitable carriers (antibodies, hormones, or lectins). The pokeweed antiviral proteins (PAP, PAP-II, and PAP- S), initially purified as inhibitors of tobacco mosaic virus synthesis, also inhibit the synthesis of both protein and viruses in cells infected with herpes simplex or poliovirus. SV40-transformed mouse fibroblasts and mouse peritoneal macrophages were 10x and 1,000x (respectively) more sensitive to PAP-S, Monomordia charantia inhibitor (MCI), or gelonin than EUE or HeLa cells and untransformed mouse fibroblasts. Nontoxic doses of PAP-S and MCI inhibited antibody formation in mice. (22 Refs) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****PLANT MOLECULAR BIOLOGY***** SCHRADER-FISCHER G APEL K CDNA-DERIVED IDENTIFICATION OF NOVEL THIONIN PRECURSORS IN VISCUM ALBUM THAT CONTAIN HIGHLY DIVERGENT THIONIN DOMAINS BUT CONSERVED SIGNAL AND ACIDIC POLYPEPTIDE DOMAINS. In: Plant Mol Biol (1993 Dec) 23(6):1233-42 ISSN: 0167-4412 The existence of new thionin variants in Viscum album has been deduced from cDNA sequences. Unlike the viscotoxins and related thionins previously found in different members of the Viscaceae, these novel thionins contain eight rather than six cysteine residues. In this respect they resemble thionins described previously from various cereals and from Pyrularia pubera, which also contain eight cysteine residues at identical positions. All of the new thionins of V. album are encoded as higher-molecular-weight precursors consisting of a signal peptide, a thionin domain and an acidic polypeptide domain. While the deduced amino acid sequences of the thionin domains of different precursor molecules are highly divergent, the two other domains are conserved among all of the variants and are distinct from the corresponding domains of thionin precursors of other plant species. Registry Numbers: 76822-96-3 (viscotoxin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****ACTA DIABETOLOGICA LATINA***** Swanston-Flatt SK Day C Bailey CJ Flatt PR Evaluation of traditional plant treatments for diabetes: studies in streptozotocin diabetic mice. In: Acta Diabetol Lat (1989 Jan-Mar) 26(1):51-5 ISSN: 0001-5563 Seven plants and a herbal mixture used for traditional treatment of diabetes were studied in streptozotocin diabetic mice. The treatments were supplied as 6.25% by weight of the diet for 9 days. Consumption of diets containing bearberry (Arctostaphylos uva-ursi), golden seal (Hydrastis canadensis), mistletoe (Viscum album) and tarragon (Artemisia dracunculus) significantly reduced the hyperphagia and polydipsia associated with streptozotocin diabetes, but bayberry (Cinnamomum tamala), meadowsweet (Filipendula ulmaria), senna (Cassia occidentalis) and the herbal mixture did not alter these parameters. Bearberry, mistletoe and tarragon retarded the body weight loss but none of the eight treatments significantly altered plasma glucose or insulin concentrations. These studies suggest that bearberry, golden seal, mistletoe and tarragon may counter some of the symptoms of streptozotocin diabetes without, however, affecting glycemic control. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****AMERICAN JOURNAL OF CHINESE MEDICINE***** Chen PM Hsiao KI Su JL Liu J Yang LL Study of the activities of Chinese herb Viscum alniformosanae Part II: The components of conditioned medium produced by Viscum alniformosanae-stimulated mononuclear cells. In: Am J Chin Med (1992) 20(3-4):307-12 ISSN: 0192-415X The human promyelocytic cell line HL-60 can be induced to monocytoid terminal differentiation by several conditioned media produced by lectin-stimulated mononuclear cells. We reported previously that a 572-conditioned medium (CM) secreted from viscum alniformosanae- stimulated mononuclear cells also had the capacity of inducing HL-60 leukemic cells into mature monocytes. In the present study, we showed that 572-CM did not contain IFN-r, TNF, IL-1 and IL-2 as determined by using ELISA tests. This CM was unable to induce granulocyte- macrophage colony formation. Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) was used to detect the components of this CM. After running the acrylamide gels, a wide band protein, in the 65-80 kd range was obtained and it was different from those of other mitogens. Registry Numbers: 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) 9008-11-1 (Interferons) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Yang LL Hsiao KI Su JL Liu J Chen PM Study of the activity of differentiation-induction in a Chinese herb- viscum alniformosanae. Part 1: In vitro induction of differentiation in HL-60 leukemic cell line by conditioned medium secreted from viscum alniformosanae-stimulated mononuclear cells. In: Am J Chin Med (1991) 19(1):33-9 ISSN: 0192-415X A conditioned medium(CM), designated as 572-CMF-, was a Chinese herb viscum alniformosanae (V.A.) stimulated mononuclear cells. This CM has the capacity to induce the promyelocytic cell line HL-60 to differentiate into morphologically and functionally mature monocytoid cells. However, our results on the effect of a combination of 572 conditioned medium and IFN-r, TNF and IL-2 were neither synergistic nor additive. Further investigation of the nature of this conditioned medium remains to be performed. Registry Numbers: 9008-11-1 (Interferons) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****ANALYTICAL AND QUANTITATIVE CYTOLOGY AND HISTOLOGY***** Kayser K Bubenzer J Kayser G Eichhorn S Zemlyanukhina TV Bovin NV Andre S Koopmann J Gabius HJ Expression of lectin, interleukin-2 and histopathologic blood group binding sites in prostate cancer and its correlation with integrated optical density and syntactic structure analysis. In: Anal Quant Cytol Histol (1995 Apr) 17(2):135-42 ISSN: 0884-6812 The binding of several biotinylated biologic probes was determined in sections of 20 surgical specimens of prostate cancer and of 21 biopsy specimens of hyperplastic prostate. Whereas neither the immunomodulatory, galactoside-specific lectin from Viscum album nor the human beta-galactoside-specific lectin (M(r) 14 kd) or its specific antibody discerned any remarkable differences, the lectin from Urtica dioica (UDA) and interleukin-2, the in vitro production of which is enhanced by this lectin, exhibited obvious preference for hyperplastic cells. In addition, the presence of binding sites for chemically synthesized blood group determinants was tested. Carcinoma cases revealed a higher percentage of binding of synthetic blood group trisaccharide H than hyperplasia cases. Due to these differences, diverse parameters, derived from measurement of integrated optical density (IOD) and from syntactic structure analysis, were correlated with the extent of binding of these biologic probes for the tumor cases. Primarily, parameters that are related to computation of a minimum spanning tree were significantly different in positive and negative cases for both UDA and interleukin- 2. For the binding of blood group trisaccharide H the 5C exceeding rate, the 2CV deviation index and the distance of neighboring tumor cells with an IOD > 5 were clearly dissimilar. Our results thus suggest an extension of the panel of biologic probes for prostate cancer and substantiate the usefulness of correlations of binding of selected biologic probes to features derived from the assessment of IOD and syntactic structure analysis. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****ANATOMY AND EMBRYOLOGY***** Zschabitz A Weiser H Stofft E Krahn V Gabius HJ Khaw A Biesalski HK Characterization of glycoconjugate expression during development of Meckel's cartilage in the rat. In: Anat Embryol (Berl) (1995 Jan) 191(1):47-9 ISSN: 0340-2061 The staining patterns of 24 biotinylated lectins were analyzed in serial sections of the mandible of 13- to 21-day-old rat embryos by means of the avidin-biotin-peroxidase method. A ubiquitous distribution of binding sites was demonstrated after incubation with Con A (Canavalia ensiformis), DSL (Datura stramonium; except bone matrix), and WGA (Triticum vulgare). ECL (Erythrina cristagalli), GSL I (Griffonia simplicifolia), SJA (Saphora japonica), VVL (Vicia villosa), DBA (Dolichus biflorus), UEA I (Ulex europeus), and LTA (Lotus tetragonobolus) were constantly negative. In early stages of development, GSL II (Griffonia simplicifolia II) was a selective marker of prechondral blastema. In contrast, PNA (Arachis hypogaea) did not stain condensing mesenchyme. During chondrogenesis of Meckels's cartilage a general decrease of lectin binding was observed. Mature cartilage matrix was constantly negative. Chondrocytes were marked by the lectins PSA (Pisum sativum), WGA, PHA- E, and PHA-L (Phaseolus vulgaris E and L). A strong GSL II binding was restricted to the mesial-superior region of the perichondrium. In later stages, several lectins revealed significant differences between preskeletal ("central") areas and the remaining ("peripheral") mesenchyme. A clear binding reaction was noted in central regions by applying LEA (Lycopersicon esculentum) and STL (Solanum tuberosum), while the peripheral tissue was only faintly stained. Developing bone was specifically marked by succinylated WGA (sWGA). The lectins LCA (Lens culinaris) and RCA (Ricinus communis) bound to fibers and extracellular matrix of the connective tissue. Jacalin (Artocarpus integrifolia) and SBA (Glycine max) binding sites were found in macrophages. Affinity of VAA (Viscum album) increased parallel with maturation of endothelial cells. Specific lectin- binding patterns revealed no correlation with the distribution of glycosaminoglycans. The results demonstrate a general reduction of oligosaccharide structures during development of Meckel's cartilage. From our observations we conclude that intralaminar glucose and/or mannose sequences as well as terminal sialic acid molecules are ubiquitously distributed, while terminal alpha-fucose was constantly negative. Lectin-binding patterns of macrophages may reflect the presence of specifically linked terminal galactose. Our findings indicate that oligosaccharides terminating in N-acetylglucosamine are bone-specific. The significance of the restricted staining of the perichondrium by GSL II remains to be elucidated. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****ANNALES PHARMACEUTIQUES FRANCAISES***** Gallego Quevedo MT Ayuso Gonzalez MJ Garcia Roman A [Subchronic toxicity of Viscum cruciatum Sieber] Toxicite subchronique de Viscum cruciatum Sieber. In: Ann Pharm Fr (1990) 48(4):192-9 ISSN: 0003-4509 (Published in French) The subchronic toxicity of an aqueous extract of Viscum cruciatum Sieber, a parasite of Prunus amygdalus Stokes, was studied in Wistar rats. The extract at dosage-levels of 30, 120 and 480 mg/kg body weight/day was administered in the drinking water during 12 weeks; checks being carried out after 4 and 8 weeks of treatment. No apparent symptoms of toxicity were observed, except for a slight apathy and reduced mobility in the batch receiving the highest dose. A slight leukopenia and a moderate increase in glycemia, uremia and plasma GPT activity was observed. No modifications occurred in the other constants studied. Histopathological analysis of the spleen, lung, kidney and liver were found to occur at the highest dosage- level, while in the other organs slight lesions of a reversible nature were observed. A certain degree of recovery was observed in the case the spleen at the end of the experiment. In all, it can be said that no manifest signs of toxicity were found in animals receiving the intermediate and higher dosages, though these were not found to be related to sex. Taken together all these observations indicate that the aqueous extract of Viscum cruciatum Sieber has a low toxicity within the conditions of our experiment. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****ANTICANCER RESEARCH***** Samal AB Gabius HJ Timoshenko AV Galactose-specific lectin from Viscum album as a mediator of aggregation and priming of human platelets. In: Anticancer Res (1995 Mar-Apr) 15(2):361-7 ISSN: 0250-7005 Galactose-specific lectin from Viscum album (VAA) was found to induce aggregation of human platelets in a dose- and sugar-dependent manner. Small nonaggregating concentrations of VAA primed the response of platelets to known aggregants (ADP, arachidonic acid, thrombin, ristocetin, and A23187). VAA-induced platelet aggregation was completely reversible by addition of the sugar inhibitor lactose and the platelets from disrupted aggregates maintained the response to other aggregants. The lectin-induced aggregation of washed platelets was more resistant to metabolic inhibitors than thrombin- or arachidonic acid-dependent cell interaction. In contrast to the related galactose-specific lectin from Ricinus communis and the soy bean agglutinin, the lectin did not aggregate liposomes prepared from total platelet lipids, indicating different affinities of aggregation- mediating lectins to platelet glycolipids. Registry Numbers: EC 3.4.21.5 (Thrombin) 26566-61-0 (Galactose) 506-32-1 (Arachidonic Acid) 63-42-3 (Lactose) 76822-96-3 (viscotoxin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Wawotzny R Andre S Dong X Joshi SS Gabius HJ Are matrix-immobilized neoglycoproteins, plant and human lectins and carbohydrate--binding antibodies from human serum mediators of adhesion in vitro for carcinoma and lymphosarcoma cells? In: Anticancer Res (1995 Jan-Feb) 15(1):169-74 ISSN: 0250-7005 Mediation of cell adhesion by defined molecules can be studied by their immobilization onto a nitrocellulose matrix and incubation with cells. In order to infer the capacity of deliberately selected protein-carbohydrate interactions to establish sugar-inhibitable cell adhesion, a panel of immobilized neoglycoproteins was employed for the murine lymphosarcoma lines RAW-117 with low (P) and high (H10) metastatic capacity, a human mammary carcinoma line (DU4475) and three human colon carcinoma lines (C205, SW480, SW620). Exhibiting an otherwise rather similar behavior relative to the line with low metastatic potential, the murine line RAW117-H10 bound strongly to the matrix with carboxyl group-bearing N-acetylneuraminic acid and glucuronic acid as well as rhamnose. Whereas the analysis of carbohydrate-mediated adhesion yielded comparable results for the three colon carcinoma lines, a markedly reduced number of adherent cells was counted for matrix-attached alpha- and beta-galactosyl, alpha-mannosyl and alpha-glucosyl moieties in the case of the mammary carcinoma line, raising evidence for cell lineage-dependent alterations of this property. From the carbohydrate-binding proteins, the plant lectin, concanavalin A and Viscum album agglutinin almost invariably served well as cell adhesion molecules. Appropriate cell surface sugar receptors, probed with neoglycoproteins, and glycoconjugates, probed with lectins, thus can contribute to adhesion in this model system. The immobilized human beta-galactoside-binding lectin (Mr 14kDa) caused adhesion of the murine lines and one colon carcinoma line (SW480). Neither C-reactive protein under conditions that induce its activity as lectin nor serum amyloid P component nor a lactose-binding immunoglobulin G fraction from human serum were reactive. However, cell adhesion to the alpha-galactoside-binding immunoglobulin G fraction of human serum was seen with the murine line of low metastatic capacity and the mammary carcinoma line. Cells of this line adhered also to the mannan-binding protein from human serum, supporting the view for its potential role in host defence against aberrantly glycosylated tumor cells. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Timoshenko AV Kayser K Drings P Kolb G Havemann K Gabius HJ Modulation of lectin-triggered superoxide release from neutrophils of tumor patients with and without chemotherapy. In: Anticancer Res (1993 Sep-Oct) 13(5C):1789-92 ISSN: 0250-7005 Superoxide production by neutrophils is believed to contribute to the efficiency of the host defence system. This activity is stimulated by the mannose-specific lectin concanavalin A, the N- acetylglucosamine/neuraminic acid-specific wheat germ agglutinin and the galactoside-specific lectins from Viscum album and human placenta. To assess whether this aspect of immune function is affected in cancer patients without or with treatment, neutrophil preparations from 69 patients were examined. Reductions in O2.(-)- production were observed for bronchial carcinoma patients after incubation with concanavalin A and the human lectin, while samples from breast cancer patients without or with treatment exhibited no significantly altered activity in the presence of each of the four agglutinins. Chemotherapy of lung and colorectal carcinoma patients reduced the neutrophilic response to concanavalin A and Viscum album agglutinin. As similarly shown for 9 specimens from other carcinoma types and from hemopoietic malignancies, there is no general impairment of responsiveness. In addition to the property of the lectin, the large extent of interindividual variation should be taken into account when it is attempted to enhance this factor of the host defence system against infections and malignant cells. Registry Numbers: 11028-71-0 (Concanavalin A) 11062-77-4 (Superoxides) 76822-96-3 (viscotoxin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Gawlik C Versteeg R Engel E Arps H Kleeberg UR Antiproliferative effect of mistletoe-extracts in melanoma cell lines (Meeting abstract). In: Anticancer Res (1992) 12(6A):1882 ISSN: 0250-7005 Extracts from the mistletoe plant (Viscum album) growing on different trees like apple, pine, oak, etc, have been suggested for treatment of different types of malignancies. Laboratory studies have shown that corean mistletoe extract possesses antitumor activity in vivo and in vitro. Here, we report on results concerning the antiproliferative effect of Viscum album C, Viscum album Qu and Viscum album M (trade name Iscador) on melanoma cell lines. Methods: Viscum album C and its constituents were received from TA Khwaja, USCLA. Constituents of Viscum album C are viscotoxin mistletoe alkaloids and three lectins (lactose-specific lectin, galactose- specific lectin, N-acetyl galactosamine-specific lectin). Viscum album Qu was extracted by Medac (Germany). Viscum album M is a preparation by the Institut Hiscia (Switzerland). The antiproliferative effect of the extracts on 11 melanoma cell lines obtained through the EORTC-MCG were tested in monolayer proliferation tests. Results: In most of the melanoma cell lines tested, there was a significant antiproliferative effect of Viscum album C at a concentration of 100 ug/ml, whereas Viscum album M showed an antiproliferative effect at 1000 ug/ml. The three lectins isolated from Viscum album C, when compared with each other, showed almost in all 11 melanoma cell lines tested a similar antiproliferative effect. It was seen at concentrations of 1-10 ng/ml. The antiproliferative effect of viscotoxin rises at concentrations of 0.5-1 ug/ml, whereas the antiproliferative effect of alkaloids begins at 10 ug/ml. Conclusions: Our data show that mistletoe extracts can have some antiproliferative effect on melanoma cell lines. The constituents of the most effective extract Viscum album C have different antiproliferative effects; a similar or even higher effect in comparison to Viscum album C could be reached using viscotoxin or alkaloids. A correlation between those in vitro activities and a possible clinical effect in vivo is difficult to define. Based on sc injections of 20 mg Viscum album M (Iscador), it appears that a 10(3) to 10(5) times higher dosage is necessary to reach comparable concentrations in man. Registry Numbers: 53986-31-5 (iscador) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****ARCHIVUM IMMUNOLOGIAE ET THERAPIAE EXPERIMENTALIS***** Paprocka M Wiedlocha A Walzel H Radzikowski C Wiedocha A The activity of two immunotoxins composed of monoclonal antibody MoAb- 16 and A-chain of ricin (MoAb-16-RTA) or A-chain of mistletoe lectin I (MoAb-16-MLIA). In: Arch Immunol Ther Exp (Warsz) (1992) 40(3-4):223-7 ISSN: 0004-069X The A-chains of ricin obtained from Ricinus communis or mistletoe lectin I from Viscum album were coupled to the monoclonal, anti- L1210V antibody MoAb-16, using SPDP as a cross linking agent. The cytotoxic activity in vitro of these immunotoxins was compared. Each of two immunotoxins tested, applied in vitro for 1 h in appropriate doses, caused irreversible inhibition of leukemic L1210 cells proliferation. Unexpectedly, MoAb-16-MLIA immunotoxin appeared to be cytotoxic to normal bone marrow progenitor cells, as observed in NCFUS tests. Moreover, this immunotoxin revealed cytotoxic effect to the P388 leukemia cells which do not share the antigen, common within L1210 leukemia cells, detected by MoAb-16 antibody. Registry Numbers: 76822-96-3 (viscotoxin) 9009-86-3 (Ricin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****ARZNEIMITTEL-FORSCHUNG***** Doser C Doser M Hulsen H Mechelke F Influence of carbohydrates on the cytotoxicity of an aqueous mistletoe drug and of purified mistletoe lectins tested on human T- leukemia cells. In: Arzneimittelforschung (1989 Jun) 39(6):647-51 ISSN: 0004-4172 Partially and highly purified lectins from Viscum album L. (mistletoe) cause a dose-dependent decrease of viability of human leukemia cell cultures, MOLT-4, after 72 h treatment. The LC50 of the partially purified lectin was 27.8 ng/ml, of the highly purified lectin 1.3 ng/ml. Compared to the highly purified lectin a 140-fold higher protein concentration of an aqueous mistletoe drug was required to obtain similar cytotoxic effects on MOLT-4 cells. Cytotoxicity of the highly purified lectin was preferentially inhibited by D-galactose and lactose, cytotoxicity of the mistletoe drug and the partially purified lectin were preferentially inhibited by lactose and N-acetyl-D-galactosamine (GalNAc). Two lectin fractions with almost the same cytotoxic activity on MOLT-4 cells but with different carbohydrate affinities were isolated by affinity chromatography from the mistletoe drug: mistletoe lectin I with an affinity to D-galactose and GalNAc and mistletoe lectin II with an affinity to GalNAc. The lectin fractions and the mistletoe drug inhibited protein synthesis of MOLT-4 cells stronger than DNA synthesis. Furthermore a subpopulation of MOLT-4, resistant to cytotoxic doses of both the mistletoe drug and the mistletoe lectins, was shown to exhibit a reduced amount of GalNAc and N-acetyl-D- glucosamine in their cellular glycoproteins which are probably responsible for the binding of the cytotoxic lectins. These results indicate that lectins are the main toxins in the mistletoe drug. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Bussing A Lehnert A Schink M Mertens R Schweizer K Effect of Viscum album L. on rapidly proliferating amniotic fluid cells. Sister chromatid exchange frequency and proliferation index. In: Arzneimittelforschung (1995 Jan) 45(1):81-3 ISSN: 0004-4172 Amniotic fluid cells (AFC) from 10 women undergoing amniocentesis were investigated. The 5-bromo-2'-deoxyuridine-induced sister chromatid exchange (SCE) frequency of AFC remained stable after the addition of a therapeutical concentration of Viscum album L. preparation Iscador P but decreased significantly after administration of high drug doses. As the proliferation index remained stable, even at extremely high drug concentrations, this effect could not be ascribed to a reduction of proliferation. No indications of cytogenetic damage or effects of mutagenicity were seen after the addition of Viscum album L. preparation P. Registry Numbers: 59-14-3 (Bromodeoxyuridine) 9007-49-2 (DNA) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Wildfeuer A Mayerhofer D [The effects of plant preparations on cellular functions in body defense] Untersuchung des Einflusses von Phytopraparaten auf zellulare Funktionen der korpereigenen Abwehr. In: Arzneimittelforschung (1994 Mar) 44(3):361-6 ISSN: 0004-4172 (Published in German) Two preparations of Echinacea purpurea and a preparation of Eleutherococcus senticosus increased the in vitro phagocytosis of Candida albicans by granulocytes and monocytes from healthy donors by 30-45%. The chemotactic migration of granulocytes in the Boyden Chamber was increased by 45% with an Echinacea purpurea extract. The two herbal preparations had no effect in either direction on intracellular killing of bacteria or yeasts. Echinacea and Eleutherococcus preparations did not induce in vitro transformation of lymphocytes. The mistel toe preparation examined (Viscum album) did not influence the tested functions of granulocytes, monocytes or lymphocytes of healthy donors. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Scheer R [The effect of mistletoe lectins on the limulus amebocyte lysate test] Beeinflussung des Limulus-Amobozyten-Lysat-Tests durch Mistel- Lektine. In: Arzneimittelforschung (1993 Jul) 43(7):795-800 ISSN: 0004-4172 (Published in German) Former reports about too high and from batch to batch changing endotoxin contents in mistletoe preparations and phytopharmaceuticals for parenteral administration correlated with clinically observed side effects led to investigations of the endotoxin content of ABNOBA- viscum. For that purpose the endotoxin levels of the raw materials, the equipment and the production steps were observed by using the limulus amebocyte lysate (LAL) test. The mean value found in the preparation containing the highest available concentration (dilution level 2 containing 15 mg of plant extract from 20 mg of fresh mistletoe in 1 ml) came to 66.7 endotoxin units (EU) per ml, corresponding to about one fifth of the commonly accepted limit value of 350 EU/ml, the human pyrogenic dose. Depending on their dilution level, lower concentrated preparations led also to lower LAL test results. It could be proved that lectins contained in mistletoe preparations cause false positive LAL tests. Such results implicate false too high contents of endotoxin. Different lysates, i.e. Limusate, Pyrogel, Pyrogent, and Pyroquant showed approximately the same results. Microbiological and LAL test results indicate that only 10% of the total amount of the LAL test result was caused by endotoxins. So it is necessary to form a new estimation of the former results of determination of the endotoxin content of mistletoe preparations. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Klett CY Anderer FA Activation of natural killer cell cytotoxicity of human blood monocytes by a low molecular weight component from viscum album extract. In: Arzneimittelforschung (1989 Dec) 39(12):1580-5 ISSN: 0004-4172 Viscum album extracts (Helixor) were investigated for their potency to influence natural killer cell (NK) cytotoxicity of human peripheral blood mononuclear cells (PBMC) in vitro. The samples investigated were unable to enhance NK cytotoxicity in PBMC/tumor cell co-cultures by direct short-term mediation but NK cytotoxicity of human PBMC was strongly stimulated when PBMC were pre-incubated for 72 h with a partly purified fraction (HM-BP) derived from extracts of V. album mali. Stimulation of NK cytotoxicity was not dependent from age and sex of PBMC donors and was directed against highly as well as moderately NK-sensitive human tumor cells. The responding effector cells were identified as monocytes/macrophages and stimulation of the NK cytotoxicity of these cells was not based on increased proliferation. The active component in the HM-BP fraction has a molecular weight of about 1000 Da or smaller and correlates with the structural criteria of an oligosaccharide. The activity was completely abrogated when the active fraction was treated with endoglycosidase F or alpha-glucosidase. Partial inactivation was observed after treatment with endoglycosidase D or hemicellulase. Moreover, the active fraction induced a reduction in tumor take incidence and tumor development in mice when applied before and after tumor challenge. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****BIOLOGICAL CHEMISTRY HOPPE-SEYLER***** Timoshenko AV Gabius HJ Efficient induction of superoxide release from human neutrophils by the galactoside-specific lectin from Viscum album. In: Biol Chem Hoppe Seyler (1993 Apr) 374(4):237-43 ISSN: 0177-3593 The immunomodulatory galactoside-specific lectin from Viscum album (VAA) induces superoxide anion (O2.-) release from human neutrophils. Among twelve tested lectins, VAA, has the highest activity, clearly surpassing the effect of the human beta-galactoside-specific lectin (galaptin). Its reactivity is blocked in the presence of lactose and is strictly dependent on the carbohydrate-binding B-subunit. The toxic A-subunit of the lectin does not elicit a response. The VAA- induced respiratory burst is less sensitive to addition of adenosine and theophylline than the concanavalin A-mediated reaction. Other modulators like amiloride (up to 100 microM), trifluoperazine and N- ethylmaleimide reveal less pronounced differences, and indomethacin, colchicine (up to 100 microM) as well as cytochalasin B act as stimulators of lectin-induced O2.- release from neutrophils. The O2.- production in the presence of small concentrations of VAA (0.1-20 micrograms/ml) is increased by addition of N-formylmethionyl-leucyl- phenylalanine (FMLP), phorbol 12-myristate 13-acetate (PMA) or digitonin, respectively, whereas concanavalin A (Con A) or wheat germ agglutinin (WGA) fail to affect the VAA-dependent extent of the respiratory burst. These results substantiate that the VAA-induced O2.- release from human neutrophils can be enhanced by other classes of inductors. Registry Numbers: 11028-71-0 (Concanavalin A) 11062-77-4 (Superoxides) 58-55-9 (Theophylline) 58-61-7 (Adenosine) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****BIOMEDICINE AND PHARMACOTHERAPY***** Timoshenko AV Cherenkevich SN Gabius HJ Viscum album agglutinin-induced aggregation of blood cells and the lectin effects on neutrophil function. In: Biomed Pharmacother (1995) 49(3):153-8 ISSN: 0753-3322 Extracts from mistletoe enjoy a large popularity in central Europe as an unconventional treatment modality for cancer, warranting scientific efforts with defined components to delineate any potential benefit. The galactose-specific lectin from Viscum album (VAA), known to exhibit immunomodulatory and ensuing antitumoral capacities in animal model systems, was shown to aggregate human blood cells in the following order: neutrophils, mononuclear cells--thrombocytes and erythrocytes. To contribute to the analysis of lectin effects on individual aspects of the host defence system, two parameters of neutrophils were quantitatively assessed, namely the aggregating activity of VAA as a measure of strength of interaction with cell surface ligands and the effect of lectin on oxidative metabolism (H2O2 release) of these cells. It was found that whole lectin and its carbohydrate-binding B-subunit possessed the capacity to induce cell aggregation and H2O2 release, which were blocked by D-galactose and lactose. Both effects displayed similar dependence on the lectin concentration in the range 0.1-25 micrograms/ml. The toxic A-subunit displayed detectable activity only in high doses (50 micrograms/ml) while the bovine heart galaptin (14 kDa; galectin-1) failed to affect neutrophils. The role of oxidative metabolism in regulation of neutrophil aggregation induced by VAA was studied using metabolic inhibitors and controlled heating at 46 degrees C leading to inhibition of plasma membrane NADPH-oxidase system. Trifluoperazine and menadione inhibited the neutrophil aggregation in a dose- dependent manner in comparison with such inhibitors as amiloride and theophylline.(ABSTRACT TRUNCATED AT 250 WORDS) Registry Numbers: 7789-20-0 (Deuterium Oxide) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****CANCER IMMUNOLOGY, IMMUNOTHERAPY***** Mueller EA Anderer FA A Viscum album oligosaccharide activating human natural cytotoxicity is an interferon gamma inducer. In: Cancer Immunol Immunother (1990) 32(4):221-7 ISSN: 0340-7004 Commercial Viscum album extract Helixor-M contains a dialysable oligosaccharide (HM-BP) that activates natural killer (NK) cytotoxicity against K562 tumour cells when preincubated with human peripheral blood mononuclear cells (PBMC) for 72 h. The activated effector cells were exclusively found in the monocyte/macrophage subpopulation. However, when peripheral non-adherent cells (PNAC) were preincubated with HM-BP for 72 h the NK cytotoxicity of CD56+CD3- NK cells was activated. This discrepancy was found to be due to the release of prostaglandin E2 from activated monocytes/macrophages, which blocked activation of the cytotoxicity of NK cells. Analysis of the supernatant culture medium after 72 h preincubation demonstrated that HM-BP induced release of interferon gamma (IFN gamma) from T cells (preferentially from CD3+CD4+ cells) and of tumour necrosis factor alpha (TNF alpha) from monocytes/macrophages. Release of IFN gamma was the crucial step for activation of NK cytotoxicity since enhancement of NK cytotoxicity during pretreatment of PBMC or PNAC with HM-BP was completely blocked in the presence of anti-IFN gamma antibodies. Anti-interleukin-2, anti-TNF alpha or anti-IFN alpha antibodies had no effect on the HM-BP-induced enhancement of NK cytotoxicity. The activation of the NK cytotoxicity of nonadherent cells by interleukin-2 treatment was found to be synergistic to the enhancement of NK cytotoxicity by treatment with HM-BP. Registry Numbers: 75882-01-8 (Helixor) 82115-62-6 (Interferon Type II) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Hauer J Anderer FA Mechanism of stimulation of human natural killer cytotoxicity by arabinogalactan from Larix occidentalis. In: Cancer Immunol Immunother (1993) 36(4):237-44 ISSN: 0340-7004 Cultures of human peripheral blood mononuclear cells (PBMC) as well as cultures of preseparated peripheral non-adherent cells (PNAC) and monocytes showed enhancement of natural killer (NK) cytotoxicity against K562 tumor cells when pretreated with arabinogalactan from Larix occidentalis for 48-72 h. Lack of enhanced responses of PBMC (37% of donors) did not necessarily mean that PNAC and monocyte cultures were also non-responsive to arabinogalactan treatment. Moreover, PBMC, PNAC and monocytes of individual donors could exhibit various responses to arabinogalactan when cultures derived from bleedings after intervals of several months were assayed. Arabinogalactan-mediated enhancement of NK cytotoxicity was not initiated directly but was found to be governed by the cytokine network. Generally, arabinogalactan pretreatment induced an increased release of interferon gamma (IFN gamma), tumor necrosis factor alpha, interleukin-1 beta (IL-1 beta) and IL-6 but only IFN gamma was involved in enhancement of NK cytotoxicity since cytotoxicity enhancement of PBMC and PNAC but not that of monocytes could be blocked when anti-IFN gamma antibodies were present during pretreatment. The presence of anti-IL-2 antibodies completely blocked NK cytotoxicity enhancement of PBMC and only moderately that of PNAC and monocytes. This blocking effect was also observed when no detectable increase of IL-2 release could be recorded. The receptor specificity of arabinogalactan is not well characterized. Initial information obtained from comparative studies indicated that arabinogalactan presumably interacts with a receptor that showed specificity for a NK-cytotoxicity-enhancing oligo-saccharide from Viscum album extracts since the action of both components was not synergistic but rather competitive. Registry Numbers: 82115-62-6 (Interferon Type II) 9036-66-2 (arabinogalactan) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Mannel DN Becker H Gundt A Kist A Franz H Induction of tumor necrosis factor expression by a lectin from Viscum album. In: Cancer Immunol Immunother (1991) 33(3):177-82 ISSN: 0340-7004 A purified lectin (MLI) from Viscum album was used to test whether peripheral monocytes from human blood can be activated for the production of tumour necrosis factor (TNF). Cytotoxic activity was detected in the supernatant of MLI-stimulated monocyte cultures. This cytotoxic activity was completely inhibited by monoclonal antibodies to TNF alpha. Small amounts of soluble TNF protein were measured in a TNF alpha-specific enzyme-linked immunospecific assay system. Strong expression of TNF alpha mRNA was induced in human monocytes as well as in macrophage cultures from C3H/HeJ mice having a low response to endotoxin after 2 h of stimulation. Both chains of the MLI were found to induce TNF mRNA equally well in human monocytes. In macrophages of endotoxin-low-responder mice the toxic A chain was a better inducer of TNF mRNA than the galactose-specific lectin B chain. Thus, MLI has immunomodulating effects in activating monocytes/macrophages for inflammatory responses. Registry Numbers: 1404-26-8 (Polymyxin B) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****CANCER LETTERS***** Ribereau-Gayon G Dumont S Muller C Jung ML Poindron P Anton R Mistletoe lectins I, II and III induce the production of cytokines by cultured human monocytes. In: Cancer Lett (1996 Dec 3) 109(1-2):33-8 ISSN: 0304-3835 The three mistletoe (Viscum album L.) lectins. ML I, ML II and ML III, were tested on their ability to enhance the secretion of the cytokines tumor necrosis factor (TNF)alpha, interleukin (IL)-1 alpha, IL-1 beta and IL-6 by human monocytes obtained from healthy donors. At lectin concentrations from 0.02 to 20/pg ml (100-10,000-fold lower than those showing toxic effects), stimulations of cytokine production several-fold over control values were observed. The immunoactivating concentrations by the three lectins were found different for each donor. At toxic concentrations, the amounts of IL- 1 alpha, IL-1 beta and to a less extent of TNF alpha in monocytes supernatants were particularly high. The data are discussed in relationship with the cytotoxic and immunoactivating effects of mistletoe lectins and their interest in cancer treatment. Registry Numbers: 76822-96-3 (viscotoxin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Bussing A Regnery A Schweizer K Effects of Viscum album L. on cyclophosphamide-treated peripheral blood mononuclear cells in vitro: sister chromatid exchanges and activation/proliferation marker expression. In: Cancer Lett (1995 Aug 1) 94(2):199-205 ISSN: 0304-3835 Based on recently published data, Viscum album L. (VAL) extracts have been shown to provide a DNA stabilizing effect which seems to be restricted to the peripheral blood mononuclear cells (PBMC). We have now investigated whether VAL exerts effects of cellular protection for phytohemagglutinin-activated PBMC treated with cyclophosphamdie (CP) in vitro. The addition of VAL resulted in a slight reduction of CP-induced sister chromatid exchanges of cultured PBMC from healthy individuals. The incubation with CP significantly reduced the expression of the low affinity interleukin-2 receptor (IL-2R alpha chain) and of transferrin receptor (TfR) on PHA-stimulated T lymphocytes. The addition of 10 micrograms/ml VAL was protective against the CP-induced depression of IL-2R alpha chain and TfR expression on these cells. The simultaneous addition of CP and purified VAL components, such as ML I, ML II/III, and viscotoxins did not significantly change expression of IL-2R alpha chain and TfR on T cells. Thus, so far undefined VAL components might be responsible for the observed protection effects of the whole plant extract. The results presented here should encourage investigation of this drug, which might become an interesting adjuvant in cancer therapy. Registry Numbers: 50-18-0 (Cyclophosphamide) 75882-01-8 (Helixor) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Kannan S Gabius HJ Chandran GJ Pillai MR Nalinakumari KR Nair MK Expression of galactoside-specific endogenous lectins and their ligands in human oral squamous cell carcinoma. In: Cancer Lett (1994 Sep 30) 85(1):1-7 ISSN: 0304-3835 Human endogenous lectins have a wide spectrum of biological functions. The present study analyses the expression of beta- galactoside specific and N-acetyl-D-galactosamine specific endogenous lectins in oral squamous cell carcinomas using biotinylated neoglycoproteins. The expression pattern of beta-galactosyl- containing glycoconjugates or ligands of beta-galactoside specific lectins in these tissues was also studied using an endogenous biotinylated lectin, the human 14-kDa lectin. For comparison a galactoside specific plant lectin from mistletoe, Viscum album was also employed. The results demonstrate that oral squamous cell carcinomas mainly express accessible binding sites for lactosylated neoglycoprotein (90%) while few carcinomas expressed mild amount of N- acetyl-D-galactosamine specific binding sites (40%). There was no difference in the binding patterns of these probes between well and less differentiated carcinomas. Expression of these neoglycoprotein binding sites were mostly concentrated in immature basaloid cells, indicating a possible association with cell proliferation. The binding pattern of D-galactosyl specific lectins (human 14-kDa and mistletoe lectins) showed conspicuous differences. This feature emphasizes the caution that needs to be exercised in interpreting the biological significance of results attained using plant lectins on human tissue. Registry Numbers: 31022-50-1 (Acetylgalactosamine) 58-85-5 (Biotin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Bussing A Suzart K Bergmann J Pfuller U Schietzel M Schweizer K Induction of apoptosis in human lymphocytes treated with Viscum album L. is mediated by the mistletoe lectins. In: Cancer Lett (1996 Jan 19) 99(1):59-72 ISSN: 0304-3835 Viscum album L. (VAL) is a phytopreparation used in adjuvant cancer therapy with both immunostimulatory and DNA stabilizing properties at low drug concentrations and cytostatic/cytotoxic properties at higher concentrations. The present work examines the cytotoxic effects of VAL extracts produced from mistletoes grown on different host trees and of purified toxic proteins from VAL, such as the D-galactose- specific lectin I (ML I), the N-acetyl-D-galactosamine-specific ML II and ML III, and crude viscotoxins towards cultured human lymphocytes. The decrease in the number of cultured lymphocytes and blast cells treated with whole plant extracts from VAL was host tree-specific. Nevertheless, there was no close correlation to the content of MLs or viscotoxins. Using the purified proteins, it became obvious that the cell killing was mediated by the induction of apoptosis, as measured by the appearance of a hypodiploid DNA peak using flow cytometry. ML III was the most effective to induce apoptosis, followed by ML II and ML I, while the viscotoxins and oligosaccharides from VAL did not. By measuring the surface expression of IL-2R alpha chains, transferrin receptors and APO-1/Fas molecules on non-apoptotic T cells, no significant changes were observed at low ML concentrations (1 ng/ml), but their decrease at higher ones. Our findings suggest that there might be at least two different ways of cell killing operative in VAL- mediated cytotoxicity: (a) the typical apoptotic cell death with the appearance of hypo-diploid nuclei, and (b) a direct or indirect killing by damaging the cell membrane with subsequent influx of Ca2+ and of the DNA intercalating dye propidium iodide and cell shrinkage. These effects might not be exclusive, as they probably occur simultaneously. Registry Numbers: 7440-70-2 (Calcium) 76822-96-3 (viscotoxin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Yoon TJ Yoo YC Choi OB Do MS Kang TB Lee SW Azuma I Kim JB Inhibitory effect of Korean mistletoe (Viscum album coloratum) extract on tumour angiogenesis and metastasis of haematogenous and non-haematogenous tumour cells in mice. In: Cancer Lett (1995 Oct 20) 97(1):83-91 ISSN: 0304-3835 We examined the inhibitory effect of an aqueous extract (referred to as KM-110) from Viscum album coloratum, a Korean mistletoe, on tumour metastasis produced by highly metastatic murine tumour cells, B16-BL6 melanoma, colon 26-M3.1 carcinoma and L5178Y-ML25 lymphoma cells, using experimental and spontaneous metastasis models in syngeneic mice. In experimental metastasis of B16-BL6 and colon 26-M3.1 cells, intravenous (i.v.) administration of KM-110 (100 micrograms/mouse) 1 day after tumour inoculation significantly inhibited lung metastasis of both tumour cells. The administration of KM-110 also exhibited a therapeutic effect on liver and spleen metastasis of L5178Y-ML25 lymphoma cells. Furthermore, in spontaneous metastasis of B16-BL6 melanoma cells, multiple administration of KM-110 into tumour-bearing mice resulted in significant inhibition of lung metastasis by tumour cells, as well as the suppressive activity to the growth of primary tumour. In in vivo analysis for tumour-induced angiogenesis, the i.v. administration of KM-110 suppressed tumour growth and inhibited the number of blood vessels oriented towards the tumour mass. In a bioassay, the culture supernatant (KM-110-treated medium) of murine peritoneal macrophages that had been stimulated with KM-110 (1-10 micrograms/ml) for 30 min followed by 24 h incubation in fresh medium showed a strong tumour necrosis factor-alpha (TNF-alpha) activity. In addition, KM-110-treated medium significantly inhibited the growth of in vitro cultures of rat lung endothelial (RLE) cells. These results suggested that the extract of Korean mistletoe inhibits tumour metastasis caused by haematogenous as well as non-haematogenous tumour cells, and that its antimetastatic effect results from the suppression of tumour growth and the inhibition of tumour-induced angiogenesis by inducing TNF-alpha. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Kuttan G Kuttan R Immunological mechanism of action of the tumor reducing peptide from mistletoe extract (NSC 635089) cellular proliferation. In: Cancer Lett (1992 Sep 30) 66(2):123-30 ISSN: 0304-3835 A peptide isolated from the Viscum album extract (Iscador) has been reported earlier to the both cytotoxic and tumour reducing. Spleen cells from animals treated with a very small quantity of this peptide were found to have increased response to phytohaemagglutinin and Concanavalin-A, indicating that more mature lymphocytes are produced by the peptide administration. Moreover injection of the peptide at the lesion site produced infiltration of lymphocytes and macrophages and finally producing necrosis of the tumor. This peptide also stimulated macrophages in vitro and in vivo and activated macrophages were found to have cytotoxic activity towards L-929 fibroblasts. Registry Numbers: 53986-31-5 (iscador) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****CARBOHYDRATE RESEARCH***** Debray H Wieruszeski JM Strecker G Franz H Structural analysis of the carbohydrate chains isolated from mistletoe (Viscum album) lectin I. In: Carbohydr Res (1992 Dec 15) 236:135-43 ISSN: 0008-6215 Two glycopeptide fractions prepared from mistletoe (Viscum album) lectin I by Pronase digestion were fractioned by affinity chromatography on a concanavalin A-Sepharose column. With 400-MHz 1H NMR spectroscopy, in conjunction with sugar analysis, the following oligosaccharide structures could be determined: two oligomannose-type glycans in the ratio 4:1, one containing six mannose and the other containing five mannose units, both with two 2-acetamido-2- deoxyglucose units. In addition, a mannotriosyl-->N,N'- diacetylchitobiose glycan containing a xylosyl group and an alpha- fucosyl group (1-->3)-linked to the 2-acetamido-2-deoxyglycosyl-1 residue, a common core element of many plant glycoproteins, was also observed. Registry Numbers: 76822-96-3 (viscotoxin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****CARCINOGENESIS***** Kuttan G Menon LG Kuttan R Prevention of 20-methylcholanthrene-induced sarcoma by a mistletoe extract, Iscador. In: Carcinogenesis (1996 May) 17(5):1107-9 ISSN: 0143-3334 Iscador, an extract from the semi-parasitic plant Viscum album, was found to inhibit 20-methylcholanthrene-induced carcinogenesis in mice. Intraperitoneal administration of Iscador (1 mg/dose) twice weekly for 15 weeks could completely inhibit 20-methylcholanthrene- induced sarcoma in mice and protect these animals from tumour-induced death. Iscador was found to be effective even at lowered doses. After administration of 0.166, 0.0166 and 0.00166 mg/dose 67, 50 and 17% of animals respectively did not develop sarcoma. Registry Numbers: 53986-31-5 (iscador) 56-49-5 (Methylcholanthrene) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ ***CHUNG HSI I CHIEH HO TSA CHIH CHINESE JOURNAL OF MODERN DEVELOPMENTS** Fu JX [Measurement of MEFV in 66 cases of asthma in the convalescent stage and after treatment with Chinese herbs] In: Chung Hsi I Chieh Ho Tsa Chih (1989 Nov) 9(11):658-9, 644 ISSN: 0254-9034 (Published in Chinese) This paper reported the measurement of maximal expiratory flow-volume curve (MEFV) for 66 cases of asthmatics in the convalescent stage. Among which the data of FEV, PEF, V75, V50, V25 in 35 cases (53.03% of the total) gave different abnormal as compared with healthy persons. It showed that in the convalescent stage, most of the asthmatics still possessed obstruction of airways and chiefly of small airways. 35 cases of asthmatics in the convalescent stage was given the Chinese herbal decoction of chiefly invigorating Kidney (Viscum coloratum 15g, Psoralea corylifolia 15g, Eucommia ulmoides 15g, Lycium chinense 9g, Tussilago farfara 15g, Artemisia capillaris 9g, and Pogostemon cablin 9g as daily dosage) for treatment of 10 weeks and measuring MEFV curves to observe their changes before and after treatment. The results showed that different parameters of MEFV was improved in some extent which suggested that the airway obstruction of asthmatics in the convalescent stage was reversible. In discussion, the authors indicated that the prompt treatment for asthmatics in the convalescent stage was conductive early to prevent emphysema and confirmed that the treatment with Chinese herbs of chiefly invigorating Kidney deserved to be propagated. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****CHUNG-KUO CHUNG HSI I CHIEH HO TSA CHIH***** Wu JX Yu GR Wang BY [Experimental study on cellular electrophysiology of Viscum coloratum flavonoid in treating tachyarrhythmias] In: Chung Kuo Chung Hsi I Chieh Ho Tsa Chih (1994 Jul) 14(7):421-3 ISSN: 1003-5370 (Published in Chinese) Viscum Coloratum Flavonoid (VCF) is one of the dihydro-flavonoids isolated and purified from the stem and leaf of Viscum Coloratum. It was proved both experimentally and clinically to have the effects of anti-tachyarrhythmias. The mechanism of this effect, however, was unclear. In this study, the effects of the drug on the fast response action potentials (FAP) in canine Purkinje fibers and guinea pig ventricular myocardial cells were investigated by glass- microelectrode technique. The results indicated that 0.1 mg/ml VCF accelerated the repolarizations of 2nd and 3rd phase of FAP, shortened action potential duration (APD), and slightly shortened effective refractory period (ERP) (canine) or unchanged (guinea pig). delta ERP/delta APD ratio was increased, therefore, ERP was relatively prolonged. All effects appeared after using the drug for 2 minutes, reached stable status after 10 minutes, and disappeared after washing off the drug for 15 minutes. It was suggested that VCF was the drug which exerted effects rapidly, maintained effects shortly, and had effects reversibly. The cellular electrophysiologic mechanisms of VCF on anti-tachyarrhythmias should be attributed to prolong the ERP relatively and abolish the reentry. This drug is particularly applicable to the tachyarrhythmias due to reentry. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****CHUNG-KUO YAO LI HSUEH PAO [ACTA PHARMACOLOGICA SINICA]***** Wu JX Yu GR Wang BY Zhong DS Huang DJ [Effects of Viscum coloratum flavonoids on fast response action potentials of hearts] In: Chung Kuo Yao Li Hsueh Pao (1994 Mar) 15(2):169-72 ISSN: 0253-9756 (Published in Chinese) The effects of the total flavonoids of Viscum coloratum (VCF) on the fast response action potentials (FAP) of canine Purkinje fibers and guinea pig ventricular papillary muscles were studied by glass- microelectrode technique. The effects of VCF on the ionic currents through cellular membrane were analysed with selective ion blockers (CsCl, verapamil, and TEA+), respectively. VCF (100 micrograms.ml-1) accelerated the repolarization of FAP and increased delta ERP/delta APD ratio, which were related to decreasing Isi and increasing Ix. It was suggested that the anti-tachyarrhythmic mechanism of VCF was attributed to prolonging ERP relatively and to abolishing reentrant excitation. Registry Numbers: 52-53-9 (Verapamil) 7440-46-2 (Cesium) 7647-17-8 (cesium chloride) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****EUROPEAN JOURNAL OF BIOCHEMISTRY***** Schrader G Apel K Isolation and characterization of cDNAs encoding viscotoxins of mistletoe (Viscum album). In: Eur J Biochem (1991 Jun 15) 198(3):549-53 ISSN: 0014-2956 Viscotoxins have been isolated from leaf homogenates of European mistletoe (Viscum album L.) and purified to apparent homogeneity. Antisera raised against these polypeptides were used to screen a cDNA expression library in lambda gt11. Two positive clones have been isolated, one encoding a full-length preprotein of viscotoxin A3 and the other encoding the precursor of viscotoxin B. Besides the viscotoxin domain the precursor contained a signal sequence and an acidic polypeptide domain. Similar higher molecular mass precursor proteins have been described for thionins of leaves and seeds of barley. Even though the acidic part of the viscotoxin precursor is much shorter than the corresponding domain of the precursors of the leaf and seed thionins of barley, both the negative charge and the number and the relative position of cysteine residues have been conserved within the acidic domain. This result is consistent with our proposal that the acidic domain of the thionin precursor may play an important role in keeping the thionin inactive within the plant cell. Registry Numbers: 24937-83-5 (Poly A) 63231-63-0 (RNA) 76822-96-3 (viscotoxin) 9007-49-2 (DNA) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****EUROPEAN JOURNAL OF CANCER***** Kovacs E Hajto T Hostanska K Improvement of DNA repair in lymphocytes of breast cancer patients treated with Viscum album extract (Iscador). In: Eur J Cancer (1991) 27(12):1672-6 ISSN: 0959-8049 We investigated alteration in DNA repair during therapy with an immunomodulator. 14 patients with advanced breast cancer were treated parenterally with Iscador, an extract of Viscum album (mistletoe). As a parameter for measurement of DNA repair the incorporation of (3H) thymidine into DNA of unstimulated lymphocytes after ultra violet light (UV) damage was taken. The DNA repair values in the patients were very low before treatment and on day 1: on average 16% of those in a healthy control population. Values started to increase on day 2 and on days 7-9 were on average 2.7 times higher than before treatment. 12/14 patients showed an improvement in repair. The values of spontaneous DNA synthesis were not altered during the treatment. We suggest that the increase of DNA repair could be due to a stimulation of repair enzymes by lymphokines or cytokines secreted by activated leukocytes or an alteration in the susceptibility to exogenic agents resulting in less damage. Registry Numbers: 50-89-5 (Thymidine) 53986-31-5 (iscador) 9007-49-2 (DNA) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Bussing A Azhari T Ostendorp H Lehnert A Schweizer K Viscum album L. extracts reduce sister chromatid exchanges in cultured peripheral blood mononuclear cells. In: Eur J Cancer (1994) 30A(12):1836-41 ISSN: 0959-8049 Increasing concentrations of Viscum album L. extracts were shown to significantly reduce sister chromatid exchange (SCE) frequency of phytohaemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC) of healthy individuals. This decrease of SCE could not be explained either by changes in lymphocyte subpopulations, by cytostatic effects of the drug or by accelerated proliferation of PHA- stimulated PBMC. Currently, no other cells tested have shown this effect. One therapeutic effect of these anti-mutagenic drugs could be a stabilisation of mononuclear blood cell DNA. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****EUROPEAN JOURNAL OF CELL BIOLOGY***** Mann KK Andre S Gabius HJ Sharp JG Phenotype-associated lectin-binding profiles of normal and transformed blood cells: a comparative analysis of mannose- and galactose-binding lectins from plants and human serum/placenta. In: Eur J Cell Biol (1994 Oct) 65(1):145-51 ISSN: 0171-9335 Surface glycoconjugates of normal and transformed blood cells are commonly characterized by plant lectins. To infer physiological significance of protein-carbohydrate interactions, mammalian lectins are obviously preferable as research tools. So far, human serum lectins have not been used to assess their binding to immunophenotyped human normal or transformed blood cells. Thus, our study combines two groups of lectins with different specificity from plant and human sources. Besides concanavalin A (ConA) we have isolated the mannose-binding protein and serum amyloid P component from human serum. Especially the mannose-binding protein is believed to play a role in host defence against bacteria and yeast cells with unknown impact on normal and tumor cells. These three lectins establish the first group. In addition to the immunomodulatory mistletoe lectin, whose binding can elicit enhanced cytokine secretion from mononuclear blood cells, we included the beta- galactoside-binding lectin (14 kDa) from human placenta in the second group. The initial series of measurements was undertaken using two- color flow cytometry to determine the phenotype-associated binding (based on cluster designation; CD) of the lectins to blood and bone marrow cells from normal donors and the cell line CEM (T- lymphoblastoid), KG1-A (primitive myeloid leukemia) and Croco II (B- lymphoblastoid). Heterogeneity was apparent for each lectin in the CD- defined cell populations. Significant differences in binding were noted between Viscum album agglutinin (VAA) and other lectins for CD4+ cells from blood and between mannose-binding protein (MBP) and VAA versus 14 kDa, ConA and serum amyloid P component (SAP) for CD19+ cells from bone marrow.(ABSTRACT TRUNCATED AT 250 WORDS) Registry Numbers: 26566-61-0 (Galactose) 31103-86-3 (Mannose) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY***** Stein G Berg PA Non-lectin component in a fermented extract from Viscum album L. grown on pines induces proliferation of lymphocytes from healthy and allergic individuals in vitro. In: Eur J Clin Pharmacol (1994) 47(1):33-8 ISSN: 0031-6970 Mistletoe preparations have been shown to express immunomodulatory properties. In order to evaluate the stimulatory potency of different mistletoe extracts, peripheral blood mononuclear cells (PBMC) from healthy and allergic/atopic individuals were exposed to aqueous or fermented extracts derived from Viscum album L. grown on apple trees (Mali-extracts) or on pines (Pini-extracts). None of them had received any mistletoe treatment. Iscador Pini was the only extract which strongly induced proliferation of PBMC in contrast to the other five preparations. On testing these extracts by Western blotting with anti-mistletoe lectin-1 (ML-1) antibody positive sera from mistletoe- treated patients, it became evident that Iscador Pini was almost devoid of lectins. The stimulatory potency of Iscador Pini for PBMC from three different groups was examined: PBMC from 35 normal controls (Group I), 23 patients with drug-induced adverse effects (Group II) and 16 individuals with allergic manifestations (Group III). Cells were exposed in 7-day cultures to the extract at concentrations between 1 and 10,000 micrograms/ml. PBMC from 63% of Group III individuals showed strong stimulation (SI varying from 6 to 97) in contrast to only 9% from Group I and 22% from Group II individuals. Anti-ML-1 antibodies were detected in 5% and anti-IP antibodies in 11% of subjects in the three groups. They were either of the IgA or IgM type but not of the IgG type. Our findings strongly imply that a non-lectin associated antigen from Iscador Pini is able to activate PBMC from healthy and allergic/atopic individuals, thereby demonstrating sensitization to probably highly conserved plant antigens. Registry Numbers: 53986-31-5 (iscador) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****FEBS LETTERS***** Peumans WJ Verhaert P Pfuller U Van Damme EJ Isolation and partial characterization of a small chitin-binding lectin from mistletoe (Viscum album). In: FEBS Lett (1996 Nov 4) 396(2-3):261-5 ISSN: 0014-5793 A novel lectin, called VisalbCBA, was isolated from European mistletoe (Viscum album). This lectin differs completely from the classical galactose/N-acetylgalactosamine-binding mistletoe lectins MLI, MLII and MLIII. Biochemical analyses indicated that VisalbCBA is a dimeric protein composed of two identical subunits of approx. 10 kDa. VisalbCBA exhibits specificity towards oligomers of N- acetylglucosamine and shows sequence homology to the previously isolated chitin-binding plant proteins. Although VisalbCBA is less toxic than the other mistletoe lectins, it definitely exhibits cytotoxic properties. The possible involvement of VisalbCBA in the biological and therapeutic effects of mistletoe is discussed. Registry Numbers: 1398-61-4 (Chitin) 76822-96-3 (viscotoxin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Endo Y Tsurugi K Franz H The site of action of the A-chain of mistletoe lectin I on eukaryotic ribosomes. The RNA N-glycosidase activity of the protein. In: FEBS Lett (1988 Apr 25) 231(2):378-80 ISSN: 0014-5793 The site of action of the A-chain of mistletoe lectin (ML-A) from Viscum album on eukaryotic ribosomes was studied. Treatment of rat liver ribosomes with ML-A, followed by treatment of the isolated rRNA with aniline, caused the release of a fragment with about 450 nucleotides from 28 S rRNA. Further analysis of nucleotide sequences of this fragment revealed that the aniline-sensitive site of phosphodiester bond was between positions A-4324 and G-4325 in 28 S rRNA. These results indicate that ML-A inactivates the ribosomes by cleaving a N-glycosidic bond at A-4324 of 28 S rRNA in the ribosomes as ricin A-chain does. Registry Numbers: EC 3.2.2. (Nucleosidases) EC 3.2.2.- (RNA N-glycosidase) 76822-96-3 (viscotoxin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Wu AM Shen F Herp A Song SC Wu JH Fraction A of armadillo submandibular glycoprotein and its desialylated product as sialyl-Tn and Tn receptors for lectins. In: FEBS Lett (1995 Feb 27) 360(2):211-5 ISSN: 0014-5793 Fraction A of the armadillo submandibular glycoprotein (ASG-A) is one of the simplest glycoproteins among mammalian salivary mucins. The carbohydrate side chains of this mucous glycoprotein have one-third of the NeuAc alpha 2-->6GalNAc (sialyl-Tn) sequence and two thirds of Tn (GalNAc alpha-->Ser/Thr) residues. Those of the desialylated product (ASG-Tn) are almost exclusively unsubstituted GalNAc residues (Tn determinant). When the binding properties of these glycoproteins were tested by a precipitin assay with Gal, GalNAc and GlcNAc specific lectins, it was found that ASG-Tn reacted strongly with all of the Tn-active lectins and completely precipitated Vicia villosa (VVL both B4 and mixture of A and B), Maclura pomifera (MPA), and Artocarpus integrifolia (jacalin) lectins. However, it precipitated poorly or negligibly with Ricinus communis (RCA1); Dolichos biflorus (DBA); Viscum album, ML-I; Arachis hypogaea (PNA), and Triticum vulgaris (WGA). The reactivity of ASG-A (sialyl-Tn) was as active as that of ASG-Tn with MPA and less or slightly less active than that of ASG-Tn with VVL-A+B, VVL-B4, HPA, WFA, and jacalin, as one-third of its Tn was sialylated. These findings indicate that ASG-A and its desialylated product (ASG-Tn) are highly useful reagents for the differentiation of Tn, T (Gal beta 1-->3GalNAc), A (GalNAc alpha 1-- >3Gal) or Gal specific lectins and monoclonal antibodies against such epitopes. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Agapov II Tonevitsky AG Shamshiev AT Pohl E Pohl P Palmer RA Kirpichnikov MP The role of structural domains in RIP II toxin model membrane binding. In: FEBS Lett (1997 Jan 27) 402(1):91-3 ISSN: 0014-5793 The interaction of plant toxin ricin and MLI binding subunits to liposomes containing monosialoganglioside (GM1), bearing a terminal galactose residue, has been examined as a possible receptor model. For the first time we demonstrate that ricin B-chain but not ricin provokes liposome aggregation at 10 M% GM1 concentration, whereas in the presence of either ricin A-chain or galactose the aggregation is inhibited. The B-subunit of plant toxin MLI from Viscum album has similar lectin specificity and activity but cannot aggregate GM1 liposomes. The ability of the B-chain to aggregate liposomes adds a new crucial step in the toxin transmembrane penetration mechanism. We demonstrate here possible ricin B-chain interactions with membranes proceeding via two sites, namely (a) a galactose-binding domain and (b) a hydrophobic interchain domain. In close contact with two phospholipid bilayers, ricin B-chain may determine the geometry of the fusion site. These events can provoke A-chain translocation which follows membrane fusion. Registry Numbers: 13699-48-4 (Dimyristoylphosphatidylcholine) 37758-47-7 (G(M1) Ganglioside) 76822-96-3 (viscotoxin) 9009-86-3 (Ricin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Citores L Ferreras JM Iglesias R Carbajales ML Arias FJ Jimenez P Rojo MA Girbes T Molecular mechanism of inhibition of mammalian protein synthesis by some four-chain agglutinins. Proposal of an extended classification of plant ribosome-inactivating proteins (rRNA N-glycosidases). In: FEBS Lett (1993 Aug 23) 329(1-2):59-62 ISSN: 0014-5793 The four chain agglutinins from Abrus precatorius, Viscum album and Ricinus communis promote depurination of the 28 S rRNA from rabbit reticulocyte ribosomes characteristic of the common ribosome- inactivating proteins (RIPs). These agglutinins inhibited mammalian protein synthesis at nanomolar concentrations but they do not affect plant protein synthesis under the same conditions. Therefore, they should also be considered as true RIPs but of a new class, the four- chain RIPs. An extended classification of RIPs is presented based on the former one from Stirpe et al. [Bio/technology 10 (1992) 405-412]. Registry Numbers: EC 3.2.2. (Nucleosidases) EC 3.2.2.- (RNA N-glycosidase) 76822-96-3 (viscotoxin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****GEMATOLOGIIA I TRANSFUZIOLOGIIA***** Timoshenko AV Cherenkevich SN [H2O2 generation and human neutrophil aggregation as affected by lectins] Generatsiia H2O2 i agregatsiia neitrofilov cheloveka pod destviem lektinov. In: Gematol Transfuziol (1995 Jul-Aug) 40(4):32-5 ISSN: 0234-5730 (Published in Russian) The effects of eight plant lectins on human neutrophils aggregation and H2O2 release were studied. Both processes were stimulated by lectins from Viscum album, Triticum vulgaris, Phaseolus vulgaris and Canavalia ensiformis while lectins from Solanum tuberosum, Sambucus nigra and Glycine mas displayed only aggregating activity and Arachis hypogaea lectin was not effective. Heating (46 degrees C) and UV- radiation during 4-5 min were found to suppress completely H2O2 release from neutrophils keeping the capacity of cells to be aggregated. The findings indicate that lectin-induced human neutrophils aggregation is necessary but not sufficient condition of respiratory burst of cells. The comparison of the aggregating activity of lectins with their ability to induce the H2O2 release is supposed to be the basis of screening of lectins with antitumor and immunomodulatory activity. Registry Numbers: 7722-84-1 (Hydrogen Peroxide) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****GLYCOBIOLOGY***** Gupta D Kaltner H Dong X Gabius HJ Brewer CF Comparative cross-linking activities of lactose-specific plant and animal lectins and a natural lactose-binding immunoglobulin G fraction from human serum with asialofetuin. In: Glycobiology (1996 Dec) 6(8):843-9 ISSN: 0959-6658 Plant and animal lectins bind and cross-link certain multiantennary oligosaccharides, glycopeptides, and glycoproteins. This can lead to the formation of homogeneous cross-linked complexes, which may differ in their stoichiometry depending on the nature of the sugar receptor involved. As a precisely defined ligand, we have employed bovine asialofetuin (ASF), a glycoprotein that possesses three asparagine- linked triantennary complex carbohydrate chains with terminal LacNAc residues. In the present study, we have compared the carbohydrate cross-linking properties of two Lac-specific plant lectins, an animal lectin and a naturally occurring Lac-binding polyclonal immunoglobulin G subfraction from human serum with the ligand. Quantitative precipitation studies of the Lac-specific plant lectins, Viscum album agglutinin and Ricinus communis agglutinin, and the Lac- specific 16 kDa dimeric galectin from chicken liver demonstrate that these lectins form specific, stoichiometric cross-linked complexes with ASF. At low concentrations of ASF, 1:9 ASF/lectin (monomer) complexes formed with both plant lectins and the chicken lectin. With increasing concentrations of ASF, 1:3 ASF/lectin (monomer) complexes formed with the lectins irrespective of their source or size. The naturally occurring polyclonal antibodies, however, revealed a different cross-linking behavior. They show the formation of 1:3 ASF/antibody (per Fab moiety) cross-linked complexes at all concentrations of ASF. These studies demonstrate that Lac-specific plant and animal lectins as well as the Lac-binding immunoglobulin subfraction from specific stoichiometric cross-linked complexes with ASF. These results are discussed in terms of the structure-function properties of multivalent lectins and antibodies. Registry Numbers: 63-42-3 (Lactose) 76822-96-3 (viscotoxin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****IMMUNOLOGICAL INVESTIGATIONS***** Kuttan G Tumoricidal activity of mouse peritoneal macrophages treated with Viscum album extract. In: Immunol Invest (1993 Aug-Oct) 22(6-7):431-40 ISSN: 0882-0139 Macrophages from mice treated with Viscum album extract were shown to be active in inhibiting the proliferation of tumour cells in culture. These activated macrophages have now been shown to protect mice from dying of progressive tumours when injected intraperitoneally into the animals. Prophylactic as well as multiple treatments with macrophages activated with Viscum album extract seemed more effective than a single treatment. The present finding suggests that in addition to a direct cytotoxic effect of Viscum album extract, the activation of macrophages may contribute to the overall antitumor activity of the drug. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Kuttan G Kuttan R Immunomodulatory activity of a peptide isolated from Viscum album extract (NSC 635 089). In: Immunol Invest (1992 Jul) 21(4):285-96 ISSN: 0882-0139 A peptide isolated from Viscum album extract (Iscador) has been earlier reported to have cytotoxic and tumour reducing activity. Administration of the peptide (2 micrograms/ml) was found to produce increased natural killer cell activity (NK-activity) in the normal animals and tumour bearing animals. The peak activity was observed on the 3rd day after the administration of the peptide. Administration of the peptide also stimulated antibody dependent cellular cytotoxicity (ADCC) which was expressed maximally on the fourth day. There was also an increase in antibody forming cells in the spleen, and antibody titers were increased in the animals treated with the peptide. Activity of the crude plant extract coincided with the activity of the peptide, indicating that the isolated peptide is mainly responsible for the immunostimulatory activity present in Viscum album extract. Registry Numbers: 53986-31-5 (iscador) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****IMMUNOLOGY LETTERS***** Tonevitsky AG Rakhmanova VA Agapov II Shamshiev AT Usacheva EA Prokoph'ev SA Denisenko ON Alekseev YuO Pfueller U The interactions of anti-MLI monoclonal antibodies with isoforms of the lectin from Viscum album. In: Immunol Lett (1995 Jan) 44(1):31-4 ISSN: 0165-2478 Monoclonal antibodies (mAb) reacting with native (TA5, TB12) and denatured (T33, T35) plant toxin mistletoe lectin I (MLI) from Viscum album have been obtained. The interaction between mAbs and native toxin with ML isoforms (MLII, MLIII) has been investigated. An immunological cross-reaction has been shown to take place for mAb TA5 (anti-A-chain of MLI) between MLII and MLIII isoforms of toxin. TA5 has not inhibited enzyme activity of the A-chain in a rabbit reticulocyte cell-free system. TB12 has been shown to react with the galactose-binding site of the B-chain. TA5 and TB12 have shown no cross-reaction with plant toxin ricin. The association constants for mAbs have been determined. The nature of heterogeneity of the lectins from Viscum album is discussed. Registry Numbers: 76822-96-3 (viscotoxin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****IMMUNOPHARMACOLOGY***** Mueller EA Hamprecht K Anderer FA Biochemical characterization of a component in extracts of Viscum album enhancing human NK cytotoxicity. In: Immunopharmacology (1989 Jan-Feb) 17(1):11-8 ISSN: 0162-3109 Enhancement of human NK cytotoxicity in the presence of fresh Viscum album extract and some commercial V. album extracts Iscador correlated strictly with an increased formation of lytic effector cell/K562 tumor cell conjugates in the single-cell assay. Both activities were completely destroyed by pretreatment of V. album extracts with pectinase, hemicellulase, amyloglucosidase and alpha- glucosidase, but not with proteases and RNase, i.e., the activities are linked to a polysaccharide. The active component in V. album extract was non-dialysable at a molecular weight cutoff of 10,000. Inhibition of both activities was observed with D-galacturonic acid, poly-galacturonic acid and pectins. The site of galacturonic acid- specific interaction could be identified on the effector cells. The rate of effector cell/tumor cell conjugate formation in the presence of V. album extracts, as well as the abrogation of both activities by pretreatment of V. album extracts with exoglycosidases specific for sugars other than galacturonic acid indicated an action of the NK cytotoxicity-enhancing component on the basis of a bridging mechanism. However, no conclusive results could be obtained for the structural specificity of the site interacting with the target cells. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****INTERNATIONAL CONFERENCE ON AIDS***** Chang RY Kong XB Meta-survey of plant and herb material as a treatment for HIV. In: Int Conf AIDS (1996 Jul 7-12) 11(1):22 (abstract no. Mo.B.303) Objective: To identify the current scope and nature of plant and herbal compounds and extracts potentially useful in anti-HIV treatment, and their state of research and development. Methods: A comprehensive search of the published literature since 1982 on all plant and herbal compounds or extracts screened for anti-HIV activity and applied to AIDS therapy, with particular attention to 1) chemical class of bioactive compounds identified, 2) ethnomedicine background, 3) mechanisms of anti-HIV actions, and 4) state of research of the compounds or extracts. Results: Tens of thousands of crude natural extracts have been screened for anti-HIV activity. Of plants and herbs screened, 70 compounds and 76 crude extracts from 123 species ranging from common food and drink (e.g. soy) to tropical rainforest specimens (e.g. Callophylum lanigerum) reportedly exhibited HIV inhibitory activity in vitro. Amongst the bioactive materials, there were 29 terpenes (15 diterpenes, 14 triterpenes), 29 flavonoids, 15 polysaccharides, 8 coumarins, 6 tannins, 4 lectins, 4 quinolones, 2 peptides, and 7 other alkaloids. Mechanisms of action elucidated included competitive and non-competitive reverse transcriptase inhibition, protease inhibition, and interference of infection at the viral cell entry level. Of bioactive species, 63 are found in the Chinese materia medica and at least another 8 are derived from other ethnomedicines. However, only a handful of such active extracts* and compounds (e.g. ganoderma*, momordica*, viscum ablbum*, curcumin, acemannan, glycyrrhizin, Lentinan, hypericin, GLQ233, PCK-4,) have been formally assessed in clinical studies of HIV patients, and most trials were observational and uncontrolled. Conclusion: Many compounds and extracts have been demonstrated to harbor HIV inhibitory activity and their elucidated mechanisms may provide valuable leads for further investigations. Only HIV inhibitory compounds or plant materials are reported here, although many more natural materials inhibit HIV and other plants or herbs may attenuate the course of HIV infection via immune enhancement, cytokine or other pathways, or act synergistically in herbal formulas and not as single species or pure componds. In all, plants and herbs offer excellent prospects in the search for potential treatment for HIV. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Gorter R Stoss M el Arif N Labonte B Beckmann C Immune modulating and anti-HIV activities of Viscum album (Iscador). In: Int Conf AIDS (1993 Jun 6-11) 9(1):496 (abstract no. PO-B28-2167) OBJECTIVES: Phase I/II study to determine safety and toxicities of Viscum album (Iscador) in HIV infection, and its potential immune modulating and anti-HIV activities. METHODS: Dose-escalating study in 40 HIV-positive patients with CD4-lymphocyte count > 200. Patients injected themselves with 0.01 mg up to 10 mg subcutaneously twice a week over a period of 18 weeks. Biweekly physical exams, surrogate markers (T-cell subsets, CD 25, HIV-p24-Ag, B2M) and other laboratory tests were obtained. RESULTS: Viscum album (Iscador) was well tolerated. No toxicities, except transient elevation of body- temperature on day of injection, and erythema on injection site were noticed; 28/36 (77%) had an increase in CD4+ lymphocytes of > or = 20% after week 12, median B2M decreased from 3.6 to 2.4 and 2/8 (25%) HIV-p24 AG positives became antigen negative. CONCLUSIONS: Viscum album (Iscador) in HIV infected patients was well tolerated and suggested to have anti-HIV activities. Registry Numbers: 53986-31-5 (iscador) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****INTERNATIONAL JOURNAL OF IMMUNOPHARMACOLOGY***** Hamprecht K Handgretinger R Voetsch W Anderer FA Mediation of human NK-activity by components in extracts of Viscum album. In: Int J Immunopharmacol (1987) 9(2):199-209 ISSN: 0192-0561 Viscum album extracts (Iscador) were investigated for their potency to influence NK cytotoxicity in vitro. In vitro short term cytotoxicity assays (4 h) with human peripheral mononuclear cells (PMNC) and human K 562 tumor cells showed a drastic enhancement of NK cytotoxicity in the presence of V. album extracts. The presence of the V. album components during tumor cell lysis was essential since preincubation of PMNC with V. album extract followed by thorough washing did not lead to enhancement of NK cytotoxicity. One responding effector cell was identified as a member of the large granular lymphocyte (LGL) family carrying both Leu 7 and Leu 11 surface markers. Furthermore, monocytes depleted of LGL, but not differentiated macrophages, showed a weak enhancement of their cytolytic activity in the presence of V. album extract. Fractionation of V. album extracts revealed two active fractions one (C1) with about 3-4000 D and the other (C2) less than 1000 D. Both components enhanced NK cytotoxicity of LGL (Leu 7+, Leu 11+) as well as of monocytes showing enhancing effects also against moderately NK- sensitive tumor cell lines. Registry Numbers: 53986-31-5 (iscador) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF ANATOMY***** Zschabitz A Krahn V Gabius HJ Weiser H Khaw A Biesalski HK Stofft E Glycoconjugate expression of chondrocytes and perichondrium during hyaline cartilage development in the rat. In: J Anat (1995 Aug) 187 ( Pt 1):67-83 ISSN: 0021-8782 Alterations in the expression of glycoconjugate structures during cartilage development in the chondrocranium, nasal skeleton, Meckel's cartilage, limb buds, vertebral bodies and ribs were investigated comparatively in 13 to 21-d-old rat embryos. The binding patterns of 24 biotinylated lectins were analysed in serial sections and compared with results obtained using histochemical methods. Proteoglycan distribution, assessed by conventional staining procedures, was not associated with lectin binding sites. During early fetal development, hyaluronate concentrations were enhanced in areas of prospective chondrogenesis. With few exceptions, the lectins showed a general increase in intensity of binding to mesenchymal structures. Con A (Canavalia ensiformis), DSL (Datura stramonium), and WGA (Triticum vulgare) displayed a ubiquitous distribution of binding sites. After incubation with LCA (Lens culinaris), PSA (Pisum sativum), STL (Solanum tuberosum), and VAA (Viscum album), characteristic differences in binding intensity between focal areas of developing mesenchyme were seen. DBA (Dolichus biflorus), ECL (Erythrina cristagalli), GSL I (Griffonia simplicifolia), LTA (Lotus tetragonobolus), SJA (Saphora japonica), UEA I (Ulex europaeus) and VVL (Vicia villosa) consistently failed to bind. During chondrogenesis a general reduction of lectin staining was detected. In early stages of development GSL II (Griffonia simplicifolia) was a specific marker of the prechondral blastema in the viscerocranium. PNA (Arachis hypogaea) selectively labelled the prevertebral blastema. In contrast, condensing mesenchyme of limb buds and viscerocranium was not stained. Using RCA (Ricinus communis), it was possible to distinguish chondroblasts from mature cells. All chondrocytes were stained by PSA, PHA-E, PHA-L (Phaseolus vulgaris E and L), and WGA, whereas Con A, LCA, and GSL II detected distinct differences between cartilage with different localisations. Cartilage matrix was constantly negative. Applying GSL II it was possible to distinguish specific segments of the perichondrium. From our results we conclude that especially high mannose oligosaccharides are amplified during development. Terminal sialic acid molecules, branched intralaminar glucose and/or mannose, respectively, internal galactose-(beta 1,4)-N-acetylglucosamine sequences as well as galactose-(beta 1,3)-N-acetylgalactosamine sequences in a preterminal position are diffusely distributed in mesenchymal tissue. In contrast, no evidence for the presence of terminal GlcNAc(beta 1,4)GlcNAc sequences and terminal alpha-fucosyl residues in (1,2) or (1,3)-linkage was obtained. Chondrogenesis appears to be correlated with a general reduction in the extent of expression of oligosaccharide structures. No proof of terminal N- acetylgalactosamine and alpha-galactose moieties was found, whereas our staining results document the expression of terminal beta- galactose structures in restricted areas of the developing mesenchyme.(ABSTRACT TRUNCATED AT 400 WORDS) Registry Numbers: 7512-17-6 (Acetylglucosamine) 9004-61-9 (Hyaluronic Acid) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF BIOLOGICAL REGULATORS AND HOMEOSTATIC AGENTS***** Bocci V Mistletoe (viscum album) lectins as cytokine inducers and immunoadjuvant in tumor therapy. A review. In: J Biol Regul Homeost Agents (1993 Jan-Mar) 7(1):1-6 ISSN: 0393-974X Therapy of cancer with a Viscum extract has been carried out in Europe for over six decades in thousands of patients with uncertain advantages. This approach has been bedeviled by major problems such as variable composition of the extract, lack of knowledge of active component(s) and mechanism of action, to cite a few. However the recent standardization of Viscumin in terms of galactoside-binding lectin activity has allowed to clarify that it can act as powerful inflammatory mediator able to stimulate the immune system. Merits and demerits of this approach have been reviewed and although the active component has probably not unique immunoenhancing properties, it may be useful as an adjuvant in the biological therapy of cancer and it should not be ignored any longer. As usual, medical progress depends upon experimentation and not exclusively on intuition and emotion. Registry Numbers: 76822-96-3 (viscotoxin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY***** Zhu HG Zollner TM Klein-Franke A Anderer FA Enhancement of MHC-unrestricted cytotoxic activity of human CD56+ CD3- natural killer (NK) cells and CD3+ T cells by rhamnogalacturonan: target cell specificity and activity against NK-insensitive targets. In: J Cancer Res Clin Oncol (1994) 120(7):383-8 ISSN: 0171-5216 Rhamnogalacturonan-mediated enhancement of MHC-unrestricted cytotoxicity was studied with freshly isolated CD56+CD3- natural killer (NK) cells, interleukin-2 (IL-2)-activated CD56+ lymphokine- activated killer (LAK) cells und IL-2/anti-CD3-activated T cells as effector cells using NK-sensitive and NK-insensitive tumor cells as targets. The rhamnogalacturonan fractions IM, IP, and IQ were prepared from commercially available extracts of Viscum album. The dose/response relation of IM, IP, and IQ demonstrated the presence of various concentrations of cytotoxicity-enhancing compounds in all three fractions that were identified as rhamnogalacturonans by degradation studies with poly-alpha-D-galacturonidase (EC 3.2.1.15) and alpha-1,6-rhamnosidase (EC 3.2.1.40). Specific cytotoxicity of all three effector cell populations as well as the respective rhamnoagalacturonan-mediated cytotoxicity enhancement was readily inhibited in a dose-dependent manner by 60%-deacetylated mannose pentaacetate. Rhamnogalacturonan-mediated enhancement of cytotoxicity of fresh CD56+ NK cells was also observed with four of five NK- insensitive tumor cells as targets, indicating that the effector- cell/tumor-cell bridging activity of rhamnogalacturonans renders NK- insensitive targets susceptible to NK-mediated lysis. Moreover, the rhamnogalacturonan-mediated cytotoxicity enhancement became even more prominent when lymphokine-activated CD56+ LAK and CD3+ T cells were assayed with the NK-insensitive tumor cell targets. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF ETHNOPHARMACOLOGY***** Kuttan G Vasudevan DM Kuttan R Effect of a preparation from Viscum album on tumor development in vitro and in mice. In: J Ethnopharmacol (1990 Apr) 29(1):35-41 ISSN: 0378-8741 The effect of Iscador, a commercial preparation made from Viscum album was studied on several cell lines using in vitro tissue culture as well as tumor-bearing animals. Iscador was found to be cytotoxic to animal tumor cells such as Dalton's lymphoma ascites cells (DLA cells) and Ehrlich ascites cells in vitro and inhibited the growth of lung fibroblasts (LB cells), Chinese hamster ovary cells (CHO cells) and human nasopharyngeal carcinoma cells (KB cells) at very low concentrations. Moreover, administration of Iscador was found to reduce ascites tumours and solid tumours produced by DLA cells and Ehrlich ascites cells. The effect of the drug could be seen when the drug was given either simultaneously, after tumour development or when given prophylactically, indicating a mechanism of action very different from other chemotherapeutic drugs. Iscador was not found to be cytotoxic to lymphocytes. Registry Numbers: 53986-31-5 (iscador) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF MOLECULAR BIOLOGY***** Sweeney EC Palmer RA Pfuller U Crystallization of the ribosome inactivating protein ML1 from Viscum album (mistletoe) complexed with beta-D-galactose. In: J Mol Biol (1993 Dec 20) 234(4):1279-81 ISSN: 0022-2836 A ribosome inactivating protein (ML1) from the mistletoe plant (Viscum album) has been crystallized. The crystals, grown in the presence of beta-D-galactose, are hexagonal, space group P6(1)22 or P6(5)22, a = b = 111.0 A, c = 309.3 A with 24 molecules per unit cell (assuming 33% solvent by weight). The protein of molecular mass 63 kDa is a heterodimer consisting of two chains, A and B, joined by a disulfide bond. The A-chain, 29 kDa, inhibits protein synthesis by depurinating an adenine residue (A4324) in a highly conserved RNA loop of the 28 S ribosomal subunit. The toxicity of the protein is mediated by the B-chain, 34 kDa, which has lectin activity, interacting with sugar residues of glycoproteins and glycolipids on the surface of target cells. Registry Numbers: 26566-61-0 (Galactose) 76822-96-3 (viscotoxin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF PROTOZOOLOGY***** De Stefano JA Cushion MT Trinkle LS Walzer PD Lectins as probes to Pneumocystis carinii surface glycocomplexes. In: J Protozool (1989 Jan-Feb) 36(1):65S-66S ISSN: 0022-3921 The binding characteristics of a panel of commercially available FITC- conjugated lectins to Pneumocystis carinii (Pc) were assessed by fluorescence microscopy and flow cytometry. Rat Pc obtained from infected lung homogenates were incubated with FITC-conjugated lectins in a series of concentrations, counterstained with propidium iodide, and analyzed for percent fluorescence and fluorescence intensity. All organisms bound concanavalin A and Wisteria floribunda agglutinin, 2 representatives of the glucose/mannose-binding group. From the lectin group specific for N-acetylglucosamine, Pc reacted more strongly with wheat germ agglutinin than with Solanum tuberosum agglutinin or Griffonia simplicifolia II lectin. Pneumocystis treated with lectins specific for N-acetyl-D-galactosamine and galactose exhibited much variation; the cells reacted moderately well to soybean agglutinin and less to Bauhinia purpurea, Maclura pomifera and Dolichos biflorus agglutinins and Griffonia simplicifolia I lectin. Arachis hypogaea agglutinin, Viscum album agglutinin and Griffonia simplicifolia I- beta 4 lectin had not effect. The organisms reacted weakly with Ulex europeus I agglutinin which is specific for fucose and did not react with Limax flavus lectin, which is specific for sialic acid. Competitive inhibition studies using relevant carbohydrates were performed to indicate that the positive reactions were specific. These studies should help to elucidate the mechanisms of attachment and pathogenesis of this organism. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****KLINISCHE WOCHENSCHRIFT***** Schultze JL Stettin A Berg PA Demonstration of specifically sensitized lymphocytes in patients treated with an aqueous mistletoe extract (Viscum album L.). In: Klin Wochenschr (1991 Jun 18) 69(9):397-403 ISSN: 0023-2173 Lymphocytes of 25 patients treated with an aqueous mistletoe extract (Viscum album L.) for up to 6 months (group 1), up to 2 years (group 2), and more than 2 years (group 3) were examined in 3- and 7-day cultures for specifically sensitized lymphocytes. The whole extract (HM), the lectin-polysaccharide fraction (HM-LP), and the 'viscotoxin' fraction (HM-V) were added at concentrations ranging from 0.5 micrograms to 12.5 mg extract/ml. Lymphocytes from four of the nine group 2 patients and five of the ten group 3 patients reacted specifically with HM and HM-LP at an optimal dose of 5.0 mg/ml, but did not react with HM-V. Stimulation indices varied between 1.6 and 16. In the patients of group 3 this effect was observed only when their lymphocytes were co-stimulated in the 3-day cultures with phytohemagglutinin (PHA), in contrast to the four patients of group 2 who reacted only in the 7-day cultures with HM-LP without PHA co-stimulation. Patients' lymphocytes had to be protected from mistletoe lectin-induced cytotoxicity by the addition of their own sera containing anti-mistletoe lectin antibodies. Lymphocytes from tumor patients (n = 18) never treated with mistletoe extracts and healthy individuals (n = 18) showed no specific proliferative response when tested in 3- and 7-day cultures.(ABSTRACT TRUNCATED AT 250 WORDS) Registry Numbers: 76822-96-3 (viscotoxin) 82115-62-6 (Interferon Type II) 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****LUNG CANCER***** Timoshenko AV Kayser K Kaltner H Andre S Gabius HJ Binding capacities of two immunomodulatory lectins, carrier- immobilized glycoligands and steroid hormones in lung cancer and the concentration of nitrite/nitrate in pleural effusions. In: Lung Cancer (1996 Feb) 14(1):75-84 ISSN: 0169-5002 Combined analysis of the binding properties of inflammatory and tumor cells in pleural effusion, and tumor imprints for various carrier- immobilized types of ligands and lectins, and of a biochemical feature of the effusions is performed to extend the characterization of these cells and their activity. In detail, the binding of Viscum album agglutinin (VAA), Urtica dioica agglutinin (UDA), and of carrier-immobilized N-acetyl-D-glucosamine (GlcNAc), lysoganglioside GM1, estradiol, progesterone, testosterone, and hydrocortisone to native specimens consisting of 46 tumor imprints from surgically treated patients with lung cancer and 74 smears of pleural effusion (PE) cells from cancer or non-cancer patients was studied using fluorescence microscopy with Texas red-labeled streptavidin. Among the tested ligands, VAA was found to provide the most effective staining of cells (60-78.1% of positive cases). When compared with inflammatory cells from PE, cancer cells were seen to bind more frequently only two ligands, namely UDA and estradiol. Significant (P < 0.001) difference between patients with bronchial carcinoma and non- cancer patients were found, when the content of NO2-/NO3- in PE fluids was measured. Whereas the level of NO2-/NO3- in PE of non- cancer patients was 12.6 +/- 10.7 microM (n = 12), it was 37.7 +/- 19.4 microM (n = 14) in cancer patients without pleural metastases and 37.5 +/- 16.0 microM (n = 26) in patients with pleural metastases. The level of NO2-/NO3- in PE appeared to correlate with extent of staining with GM1 and GlcNAc: in non-cancer patient groups it was significantly higher (P = 0.032) for negative subjects than those binding the ligand GlcNAc, whereas in the patient group with adenocarcinoma it was significantly lower (P = 0.032) for patients without binding capacities for GlcNAc and GM1. The results obtained suggest that the combined analysis of increased levels of NO2-/NO3- in PE and of glycohistochemical properties of cancer and inflammatory cells may be useful in exploring the interrelationship of functionally important cellular characteristics. Registry Numbers: 10102-43-9 (Nitric Oxide) 37758-47-7 (G(M1) Ganglioside) 7512-17-6 (Acetylglucosamine) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****MOLEKULIARNAIA BIOLOGIIA***** Tonevitskii AG Rakhmanova VA Shamshiev AT Usachaeva EA Agapov II Prokov'ev SA Denisenko ON Pfuller U Eifler R [Study of plant lectins from Viscum album using monoclonal antibodies] Issledovanie rastitel'nykh lektinov iz omely beloi s pomoshch'iu monoklonal'nykh antitel. In: Mol Biol (Mosk) (1995 May-Jun) 29(3):619-26 ISSN: 0026-8984 (Published in Russian) Monoclonal antibodies (monAT) against both native (TA5, TB12) and denatured (TB33, TB35) plant toxin ML1 from Viscum album have been obtained. The interaction of monAT against native toxin with its isoforms ML2 and ML3 was investigated. It was shown that monAT TA5 to A-chain of ML1 toxin cross-reacted with ML2 and ML3 isoforms. TA5 did not inhibit enzyme activity of A-chain in cell-free rabbit reticulocyte system. It was shown that monAT TB12 reacted with galactose-binding site of B-subunit. Both monAT had no cross- reactions with plant toxin ricin. The binding constants for TA5 with ML1, ML2, ML3 respectively were 4.3.10(7) M-1, 1.2.10(7) M-1, and 0.3.10(7) M-1. The binding constants for TB12 were 2.10(7) M-1 with ML1 toxin, and more than 10(6) M-1 with ML2 and ML3. The nature of heterogeneity in ML toxin family is discussed. Test-systems for ML1 determination in different V. album extracts are suggested. Registry Numbers: 9009-86-3 (Ricin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****MOLECULAR AND CELLULAR BIOCHEMISTRY***** Zeng FY Benguria A Kafert S Andre S Gabius HJ Villalobo A Differential response of the epidermal growth factor receptor tyrosine kinase activity to several plant and mammalian lectins. In: Mol Cell Biochem (1995 Jan 26) 142(2):117-24 ISSN: 0300-8177 Biosignalling via lectins may involve modulation of protein kinase activities. This aspect of the biological action of mammalian and plant lectins has been investigated for their effect on the activity of the isolated epidermal growth factor receptor (EGFR). The constitutive tyrosine kinase activity of the epidermal growth factor receptor from rat liver, isolated by calmodulin-affinity chromatography, was activated by concanvalin A (ConA), and wheat germ agglutinin (WGA) to a similar extent as the measured enhancement induced by EGF. In contrast, two mannose-specific lectins, the mannan- binding protein (MBP) and serum amyloid P component (SAP), isolated from human serum, have inhibitory effects, both in the absence and presence of EGF. The differential effects of these lectins were tested using as phosphorylatable substrates a co-polymer of glutamic acid-tyrosine, as well as calmodulin. However, two galactoside- specific lectins, the laminin-binding beta-galactoside-binding 14 kDa lectin, isolated from bovine heart (14K-BHL), and the alpha/beta- galactoside-binding lectin, isolated from mistletoe (Viscum album L.) leaves (VAA), do not inhibit the EGFR tyrosine kinase activity. The sugar dependence of the lectin-mediated action was studied by inhibition assays. Mannose and a mannose-containing neoglycoprotein prevent the activating effect of ConA, and N-acetyl-D-glucosamine partially prevents the activation produced by WGA. However, mannose and mannose-containing neoglycoprotein were ineffective to reduce the inhibitory effect of MBP or SAP.(ABSTRACT TRUNCATED AT 250 WORDS) Registry Numbers: EC 2.7.1.112 (Protein-Tyrosine Kinase) 11028-71-0 (Concanavalin A) 31103-86-3 (Mannose) 56-65-5 (Adenosine Triphosphate) 62229-50-9 (Epidermal Growth Factor-Urogastrone) 7512-17-6 (Acetylglucosamine) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****MOLECULAR IMMUNOLOGY***** Wu AM Shen F Herp A Wu JH Interaction of hamster submaxillary sialyl-Tn and Tn glycoproteins with Gal, GalNAc and GlcNAc specific lectins. In: Mol Immunol (1994 Apr) 31(6):485-90 ISSN: 0161-5890 Hamster submaxillary glycoprotein (HSM), one of the simplest glycoproteins among mammalian salivary mucins, is composed of approximately equivalent amounts of protein, hexosamine and sialic acid. The Thr and Ser residues in the protein core account for more than half of all of the amino acid residues, while Lys, Glu, Pro and Ala are the major components of the remaining portion of amino acids. The carbohydrate side chains of this mucous glycoprotein have mainly the NeuAc-GalNAc-(sialyl-Tn) sequence (HSM), and those of the desialylated product (HSM-Tn) are almost exclusively unsubstituted GalNAc residues (Tn determinants). The binding properties of sialyl- Tn (HSM) and asialo-HSM (HSM-Tn) glycoproteins were tested by precipitin assay with Gal, GalNAc and GlcNAc specific lectins. The HSM-Tn completely precipitated Vicia villosa (VVL both B4 and mixture of A and B), Maclura pomifera (MPL), and Artocarpus integrifolia (Jacalin) lectins; less than 2 micrograms of HSM-Tn were required for precipitating 50% of 5.0-6.3 micrograms lectin nitrogen added. HSM-Tn also reacted well with Helix pomatia lectin (HPL), Wistaria floribunda lectin (WFL) and Abrus precatorius agglutinin (APA) and precipitated in each case over 81% of the lectin nitrogen added. The reactivity of HSM-Tn with other lectins (Ricinus communis, RCA1; Dolichol biflorus, DBL; Viscum album, ML-I; Arachis hypogaea, PNA, and Triticum vulgaris, WGA) was weak or negligible. The activity of sialyl-Tn (HSM) was more restricted; HSM reacted well with Jacalin, moderately with MPL and VVL-B4, but was inactive or only weakly with the other lectins used. These findings indicate that HSM and its desialylated product (HSM-Tn) are highly useful reagents for the differentiation of Tn and T/Gal specific lectins and for anti-T, Tn and Af monoclonal antibodies. Registry Numbers: 131-48-6 (N-Acetylneuraminic Acid) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****NATURAL IMMUNITY***** Hostanska K Hajto T Spagnoli GC Fischer J Lentzen H Herrmann R A plant lectin derived from Viscum album induces cytokine gene expression and protein production in cultures of human peripheral blood mononuclear cells. In: Nat Immun (1995 Sep) 14(5-6):295-304 ISSN: 1018-8916 A plant lectin from Viscum album (ML-I) has been shown to increase the number and cytotoxic activity of natural killer cells and to induce antitumor activity in animal models. However, the mechanisms underlying the effects of ML-I on natural host defenses are unknown. After 24 h incubation of peripheral blood mononuclear cells in the presence of 10 and 1 ng/ml of ML-I, mRNA expression and secretion of a panel of cytokines were evaluated by reverse polymerase chain reaction and by ELISA, respectively. The lectin induced expression of interleukin (IL)-1 alpha, IL-1 beta, IL-6, tumor necrosis factor- alpha, interferon-gamma, granulocyte-monocyte colony-stimulating factor and IL-10 genes but no expression of IL-2 and IL-5 genes could be detected. Regarding cytokine secretion, IL-6 and TNF-alpha production was induced by 10 ng/ml ML-I. On the other hand, IL-10 secretion was only stimulated by 1 ng/ml lectin. No production of IFN- gamma or, as expectable, IL-2 could be detected. In addition, ML-I increased the percentage of HLA-DR+ T lymphocytes in vitro. In tests performed on whole blood, monocytes and granulocytes bound the fluorescence-conjugated ML-I molecules to a higher degree than lymphocytes. Expression of IL-1 beta and IFN-gamma genes could also be observed upon ML-I stimulation of nonadherent cells. These results suggest that lectin-sugar interactions on the cell surface of immunocompetent cells can induce cytokine gene expression and protein synthesis. Registry Numbers: 76822-96-3 (viscotoxin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY***** Wenzel-Seifert K Lentzen H Seifert R In U-937 promonocytes, misteltoe lectin I increases basal [Ca2+]i, enhances histamine H1- and complement C5a-receptor-mediated rises in [Ca2+]i, and induces cell death. In: Naunyn Schmiedebergs Arch Pharmacol (1997 Feb) 355(2):190-7 ISSN: 0028-1298 Mistletoe lectin I (ML I) from Viscum album inhibits cell growth and induces apoptosis (programmed cell death) in several cell types. Because increases in cytosolic Ca2+ concentration ([Ca2+]i) constitute a signal for the induction of apoptosis, we studied the effects of ML I on basal [Ca2+]i, receptor-mediated rises in [Ca2+]i and cell viability, using human U-937 promonocytes as model system. Treatment of U-937 cells with ML I (30-100 ng/ml) significantly increased basal [Ca2+]i. ML I (10-30 ng/ml) enhanced histamine- induced rises in [Ca2+]i up to five-fold. The effect of histamine was inhibited by clemastine but not by famotidine, indicative for its mediation via H1-receptors. ML I additionally enhanced the stimulatory effect of complement C5a on [Ca2+]i, whereas the effect of ATP was unaffected. ML I did not induce responsiveness of U-937 cells towards a bacteria-derived chemotactic peptide. ML I up to 10 ng/ml did not affect cell viability and growth of U-937 cells. ML I at 30 ng/ml moderately inhibited cell growth and reduced cell viability. At 100 ng/ml, ML I was strongly cytotoxic. Our data support the view that Ca2+ plays a role as intracellular signal molecule in the induction of apoptosis and point to an accelerating role of H1- and C5a-receptors in the regulation of this process. Registry Numbers: 7440-70-2 (Calcium) 76822-96-3 (viscotoxin) 80295-54-1 (Complement 5a) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****ONCOLOGY***** Jordan E Wagner H Structure and properties of polysaccharides from Viscum album (L.). In: Oncology (1986) 43 Suppl 1:8-15 ISSN: 0030-2414 Polysaccharides are possibly involved in the pharmacological effects of Viscum album (mistletoe) extracts, which are used in cancer therapy. Therefore the water-soluble polysaccharides of the fresh plant and the fermented proprietary preparation Iscador were isolated and characterized inter alia by methylation analysis, partial hydrolysis and C-13-NMR spectroscopy. The main polysaccharide of the green parts of Viscum is a highly esterified galacturonan whereas in Viscum 'berries' a complex arabinogalactan is predominant. Both types of these constituents were found in Iscador but with definite changes in molecular weight and structure. An interaction between the arabinogalactan and the galactose-specific lectin (ML I) in Viscum could be demonstrated. In three immunological tests (granulocyte, chemiluminescence, carbon clearance test) the polysaccharides failed to increase phagocytic activity of granulocytes and macrophages. Registry Numbers: 53986-31-5 (iscador) 7440-44-0 (Carbon) 76822-96-3 (viscotoxin) 9036-66-2 (arabinogalactan) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Hajto T Immunomodulatory effects of iscador: a Viscum album preparation. In: Oncology (1986) 43 Suppl 1:51-65 ISSN: 0030-2414 The immunomodulatory effects of Iscador (a mistletoe, Viscum album extract) were investigated. After a single intravenous infusion of Iscador several immunological parameters in the peripheral blood of breast cancer patients were examined. Parallel with neutrophilia, and with an increase of juvenile neutrophils, a significant enhancement of phagocytic activity of granulocytes was shown. After short decreases during the first 24 h, significant increases in natural killer (NK) and antibody-dependent cell-mediated cytotoxicity (ADCC) activities as well as augmented levels of large granular lymphocytes were observed. These NK/ADCC responses followed a kinetic pattern similar to that after treatment with alpha-interferon described by others. Further significant increases in mitogenic responses to phytohemagglutinin and concanavalin A were observed. Registry Numbers: 53986-31-5 (iscador) 9008-11-1 (Interferons) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Becker H Botany of European mistletoe (Viscum album L.). In: Oncology (1986) 43 Suppl 1:2-7 ISSN: 0030-2414 European mistletoe (Viscum album L.) is a hemiparasitic plant growing on different host trees. According to host specifity three different races can be distinguished. The plant is dioecious with very reduced male and female flowers. The life cycle of V. album is described starting from seed germination to the development of the leaves. The parasitism affords special adaptation to mineral nutrition. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Hajto T Lanzrein C Natural killer and antibody-dependent cell-mediated cytotoxicity activities and large granular lymphocyte frequencies in Viscum album- treated breast cancer patients. In: Oncology (1986) 43(2):93-7 ISSN: 0030-2414 20 breast cancer patients received a single intravenous infusion of Iscador, a mistletoe (Viscum album L.) extract. Natural killer (NK) and antibody-dependent cell-mediated cytotoxicity (ADCC) activities as well as the number of large granular lymphocytes (LGL) were investigated in their peripheral blood at various times. Six hours after the start of the infusion, significant decreases and 24 h later, significant increases in NK/ADCC activities and LGL frequencies were observed. These responses followed a kinetic pattern similar to that which has been described by others to occur after treatment with interferon. Registry Numbers: 53986-31-5 (iscador) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Jurin M Zarkovic N Hrzenjak M Ilic Z Antitumorous and immunomodulatory effects of the Viscum album L. preparation Isorel. In: Oncology (1993 Nov-Dec) 50(6):393-8 ISSN: 0030-2414 There are numerous data on the immunostimulative and antitumorous activity of various Viscum album tissue extracts. Isorel (Novipharm, Austria) is one of these compounds. We found that in mice an increased number of plaque-forming cells to sheep red blood cells (SRBC) followed the injection of Isorel together with SRBC. Further, survival time of a foreign skin graft was shortened if Isorel was applied at the correct time. Finally, suppressed immune reactivity in tumorous mice recovered following Isorel injection. Isorel was further shown to be cytotoxic to tumor cells in vitro. Its application to tumor-bearing mice could prolong their life but without any therapeutic effect. However, a combination of local irradiation and Isorel was very effective: following 43 Gy of local irradiation to a transplanted methylcholanthrene-induced fibrosarcoma (volume about 240 mm3) growing in syngeneic CBA/HZgr mice, the tumor disappeared in about 25% of the animals; the addition of Isorel increased the incidence of cured animals to over 65%. The combined action of Isorel, influencing tumor viability on the one hand and the host's immune reactivity on the other, seems to be favorable for its antitumor action in vivo. Registry Numbers: 56-49-5 (Methylcholanthrene) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****ONKOLOGIE***** Coeugniet EG Elek E Immunomodulation with Viscum album and Echinacea purpurea extracts. In: Onkologie (1987 Jun) 10(3 Suppl):27-33 ISSN: 0378-584X Extracts of Viscum album (Plenosol) and Echinacea purpurea (Echinacin) are used clinically for their non-specific action on cell- mediated immunity. In vitro we could prove that these two extracts have a stimulating effect on the production of lymphokines by lymphocytes and in the transformation test. A toxic effect on cells was produced only with very high, clinically irrelevant concentrations. Clinical application of these extracts can produce a stimulation of cell-mediated immunity (one therapeutic administration followed by a free interval of one week) or can have a depressive action (daily administrations of higher doses). These observations were confirmed by lymphokine production and assay, 3H-thymidine incorporation and a skin test with recall antigens (Multitest Merieux). €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Coeugniet EG Assay of the cell-mediated immunity in patients with malignant and non-malignant diseases. In: Onkologie (1987 Jun) 10(3 Suppl):22-6 ISSN: 0378-584X The depression of cell-mediated immunity (CMI) was determined in patients with ovarian and breast carcinomas by lymphokine production under Con-A-stimulation (migration inhibitory factor), T-lymphocyte- transformation test under PHA-stimulation and with a skin reactivity test with a viscum album extract (Plenosol, Dr. Madaus, Cologne, FRG). The results show a good correlation between the different types of CMI function tests. The cytostatics have a depressive effect on CMI more through a cumulative effect than through the actual concentration. Some of the patients with chronic rheumatism who were not treated were anergic, and that also had an influence on the therapy. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****PHARMAZIE***** Yoshida T Zhang M Chen C Franz H Wu HC Enhancement of the cytotoxicity of mistletoe lectin-1 (ML-1) by high pH or perturbation in Golgi functions. In: Pharmazie (1991 May) 46(5):349-51 ISSN: 0031-7144 We have studied the cytotoxicity of Mistletoe lectin-1 (ML-1), a cytotoxic protein produced by Viscum album, in CHO and V79 cells and in mutant cell lines altered in Golgi functions or in endosomal acidification. In wild-type CHO cells, cytotoxicity of ML-1 was greatly enhanced by ammonium chloride or nigericin. A CHO mutant defective in endosomal acidification (DMPR-2), which is resistant to diphtheria toxin, modeccin and Pseudomonas aeruginosa exotoxin A and hypersensitive to ricin, showed increased sensitivity to ML-1. MonR- 31 and MF-1 are monensin- and compactin-resistant mutants derived from CHO and V79 cell lines, respectively, and are presumably altered in Golgi functions. The cytotoxicity of ML-1 was found to be increased in both MonR-31 and MF-1 cells as compared with their parental cells. These results indicate that the effects of chemicals or mutations altering endosomal acidification and Golgi functions on the cytotoxicity of ML-1 are similar to those on ricin cytotoxicity. Our results suggest that the cytotoxicity of ML-1 is enhanced by an increase in endosomal pH, as well as by chemicals or mutations altering the structure/functions of the Golgi regions. Like ricin, the intoxication process of ML-1 may involve the Golgi regions. Registry Numbers: 12125-02-9 (Ammonium Chloride) 28380-24-7 (Nigericin) 76822-96-3 (viscotoxin) 9009-86-3 (Ricin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Metzner G Franz H Kindt A Schumann I Fahlbusch B Effects of lectin I from mistletoe (ML I) and its isolated A and B chains on human mononuclear cells: mitogenic activity and lymphokine release. In: Pharmazie (1987 May) 42(5):337-40 ISSN: 0031-7144 The interaction of lectin I from mistletoe (Viscum album) (ML I) and its isolated A and B chains with mononuclear cells from healthy human donors was investigated with respect to proliferation capacity (mitogenicity) and monokine/lymphokine factor (MSF) production. The factor produced was studied by means of the electrophoretic mobility inhibition assay using guinea pig macrophages as indicator cells. ML I and its B chain exhibited comparable inhibitory effects on the proliferation of mononuclear cells (MNC, lymphocytes) that differed in quantity only. After 72 h the tritiated thymidine incorporation had diminished in comparison to the control over a concentration range from 10(-7) to 10(-11) mol/l (ML I) or from 3 X 10(-7) to 3 X 10(-9) mol/l (B chain), respectively. The ML I was about 30 times more active than the B chain. Moreover, MSF production could be substantiated for the B chain at a concentration of 3 X 10(-8) mol/l. In contrast to the B chain, the A chain stimulated the MNC to blastogenic transformation at concentrations of 3 X 10(-8) and 3 X 10(-9) mol/l. The stimulation index was much lower than after PHA stimulation. The same concentrations induced the production of lymphokine (MSF). The lymphokine activity on the indicator cells could be inhibited by L-fucose. Perhaps both cytotoxicity and lymphocyte stimulation are important for anti-tumor activity after application in vivo. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****PLANTA MEDICA***** Schmidt KH [Studies on the effect of mistletoe extract on the chemotactic activity and on chemiluminescence of polymorphonuclear leukocytes in vitro] Untersuchungen zur Wirkung von Mistelextrakt auf Chemotaxis und Chemilumineszenz polymorphkerniger Granulocyten in vitro. In: Planta Med (1989 Oct) 55(5):455-7 ISSN: 0032-0943 (Published in German) In the present study, the chemotactic activity of human polymorphonuclear granulocytes was measured using the tripeptide N-F- Met-Leu-Phe and different concentrations of extracts of Viscum album as chemotactic stimuli. It turned out that the extracts have the capability of stimulating chemotaxis up to 30% of the formylated tripeptide. Incubation of isolated granulocytes for 20 minutes in medium alone prior to assessment of chemotaxis results in a 20% loss of chemotactic activity as compared to the freshly isolated cells. Incubation in a medium containing the mistletoe extract does not result in partial deactivation of chemotaxis. This protective effect of the plant extract can be interpreted on the basis of an interaction with the oxidative metabolism of the granulocytes causing partial self-deactivation of chemotaxis. Interference of the extract of Viscum album with the oxidative metabolism of phagocytes is shown in experiments with luminol enhanced chemiluminescence stimulated by opsonized zymosan. The data show a dose-dependent decline of photon emission in the presence of the extracts. The in vitro data measured in the present study provide additional evidence of an immunomodulatory effect of extracts of Viscum album from which in vivo therapeutic effects can be expected. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Timoshenko AV Gabius HJ Influence of the galactoside-specific lectin from Viscum album and its subunits on cell aggregation and selected intracellular parameters of rat thymocytes. In: Planta Med (1995 Apr) 61(2):130-3 ISSN: 0032-0943 Galactose-specific lectin from Viscum album (VAA) was shown to induce the aggregation of rat thymocytes, to increase the intracellular Ca(2+)-availability, and to enhance the menadione-dependent release of H2O2 from cells in a carbohydrate- and dose-dependent manner. This activity was mediated by the carbohydrate-binding B-subunit, whereas the toxic A-subunit failed to display aggregating activity or to affect the intracellular Ca2+. However, incubation of cells in its presence decreased the release of H2O2. These data extend the knowledge of the immunomodulatory potency of VAA, especially its carbohydrate-binding B chain. Registry Numbers: 7440-70-2 (Calcium) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****RADIOBIOLOGIIA***** Narimanov AA Popova OI Murav'eva DA [Changes in the sensitivity of mice to the action of gamma irradiation by Viscum album L. polysaccharides] Izmenenie chuvstvitel'nosti myshei k deistviiu gamma-radiatsii s pomoshch'iu polisakharidov omely beloi (Viscum album L.). In: Radiobiologiia (1992 Nov-Dec) 32(6):868-72 ISSN: 0033-8192 (Published in Russian) The influence of water-soluble polysaccharides of Viscum album L. on the survival of mice subjected to whole-body gamma-irradiation has been investigated. Polysaccharides were shown to exert a radioprotective effect which was a function of both the radiation dose and the drug dose and time of its injection. The maximum radioprotective efficacy of polysaccharides was observed after their injection 15 min before irradiation. A single intraperitoneal administration of polysaccharides (25 mg/kg) before irradiation with LD50/30 and LD100/10-12 increased the 60-day survival rate up to 95% and 27% respectively. The postirradiation injection of polysaccharides prevented death of 80% of mice given LD50 and increased the average life expectancy of animals irradiated with absolutely lethal doses. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****RESEARCH IN EXPERIMENTAL MEDICINE***** Timoshenko AV Kayser K Drings P Andre S Dong X Kaltner H Schneller M Gabius HJ Carbohydrate-binding proteins (plant/human lectins and autoantibodies from human serum) as mediators of release of lysozyme, elastase, and myeloperoxidase from human neutrophils. In: Res Exp Med (Berl) (1995) 195(3):153-62 ISSN: 0300-9130 Analysis of cell surface glycosylation not only provides information about cell properties such as their state of differentiation or histogenetic lineage. The carbohydrate chains also provide potentially functional binding sites to endogenous carbohydrate- binding proteins. This interaction can elicit consequent signalling processes. Because of the importance of neutrophils in the host defence system, we monitored the effect of the binding of such sugar receptors to their cell surface on the release of the enzymatic activities of lysozyme, elastase, and myeloperoxidase. Besides the mannose-binding lectin concanavalin A and the immunomodulatory alpha/beta-galactoside-binding lectin from Viscum album L., three preparations of human sugar receptors - beta-galactoside-binding lectin (M(r) 14 kDa) and two affinity-purified polyclonal IgG fractions from serum with the capacity to recognize alpha- or beta- galactosides, respectively - were used. Two animal lectins from chicken liver and intestine that bind beta-galactosides, as well as the lectin-like human serum amyloid P component, were included in order to assess the importance of slight differences in ligand recognition. Cytochalasin B-enhanced enzyme release was invariably seen with the two plant lectins and the chicken liver beta- galactoside-binding lectin, but the related intestinal lectin did not increase enzyme release. The mammalian homologue of these avian lectins triggered lysozyme secretion, and the lactoside-binding IgG fraction enhanced the amount of extracellular elastase activity slightly but significantly. Thus, the actual lectin, not the nominal specificity of sugar receptors, is crucial for elucidation of responses. Due to the highly stimulatory activity of the two plant lectins, neutrophils from patients with non-cancerous diseases and from patients with lung cancer were monitored for the extent of lectin-mediated enzyme release. Only the concanavalin A-mediated reactivity of the neutrophils was associated with the type of disease. Registry Numbers: EC 1.11.1.7 (Peroxidase) EC 3.2.1.17 (Muramidase) EC 3.4.21.36 (Pancreatopeptidase) 11028-71-0 (Concanavalin A) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****SCHWEIZERISCHE RUNDSCHAU FUR MEDIZIN PRAXIS***** Kast A Hauser SP [Iscucin--mistletoe preparations for the pre- and postoperative treatment of malignancies. Documentation No. 21] Iscucin--Mistelpraparate fur die pra- und die postoperative Malignombehandlung. Dokumentation Nr. 21. In: Schweiz Rundsch Med Prax (1990 Apr 3) 79(14):427-9 ISSN: 0369-8394 (Published in German and Russian) Iscucin-Viscum preparations contain mistletoe from eight different host-trees and are produced according to a particular 'rhythmic' procedure and additionally 'potentialized'. Sterilization should be achieved by the addition of oligodynamic silver. The indications given are: precancerous conditions, postoperative tumour prevention, operable tumours, and inoperable tumours. Each of the eight preparations (according to host-tree) has its own list of indications. Iscucin is supposed to be injected close to the tumour between 5 and 7 p. m.; the dosage and the frequency depend on body temperature. The annual costs of Iscucin treatment are DM 140.- to 280.-, not including doctor's visits, homeopathic drugs and special diet. Koehler began to develop Iscucin in 1958 on the basis of a personal communication of Steiner made in 1924. It is produced and distributed by Wala-Heilmittel GmbH, Eckwalden. Most Wala publications have been written by H. H. Vogel, the medical advisor of Wala. Vogel combines Fromme's mesenchymal theories with the anthroposophical ideas on carcinoma development in that he designates the mesenchyma as the organic vehicle of the 'ethereal body' (Atherleib). Carcinomas develop on depletion of the mesenchymal forces; mistletoe, on the other hand, activates the mesenchyma. No preclinical or clinical investigations are available. However, the performance of controlled clinical studies is hardly possible, since the supportive measures considered to be essential cannot be applied according to a specific schedule. Iscucin is not registered in Switzerland at the IKS. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****TERATOGENESIS, CARCINOGENESIS, AND MUTAGENESIS***** Basaran AA Yu TW Plewa MJ Anderson D An investigation of some Turkish herbal medicines in Salmonella typhimurium and in the COMET assay in human lymphocytes. In: Teratog Carcinog Mutagen (1996) 16(2):125-38 ISSN: 0270-3211 Medicinal plants play a major role in the life of Turkish people and of late medicinal plant usage has increased in many countries. Green plants in general contain mutagenic and carcinogenic substances, but there is little information about the biological activities of herbal medicine. In the present study, therefore, various Turkish medicinal herbs were investigated for their genotoxic potential in the Salmonella typhimurium microsomal activation assay and the alkaline single cell gel electrophoresis (COMET) assay. Extracts from these medicinal herbs and some fractions of these extracts were examined. The species investigated were Arctium minus, Ecballium elatterium, Momordica charantia, Plantago major, Urtica dioica, Viscum album, Salvia triloba, Euphorbia rigida, Stachys lavandulifolia, Acteoside, Abies nordmannia. They are used for various immune disorders and are applied either topically or taken orally as a herbal tea. Of the 19 samples of the extracts and fractions investigated, none produced a positive response in strains TA98 and TA100 with or without metabolic activation, but all produced an increase above negative control values in the COMET assay. Some extracts were investigated further and produced dose-related increases. In the case of Urtica and Euphorbia species, where two fractions from these plants were examined, one fraction produced a greater response than the other. It is suggested that the lesser response of the fractions might be due to less DNA strand-breaking agents in the fractions or they may have antigenotoxic properties. The breaks that are detected in the COMET assay could be alkali-labile AP-sites and intermediates in base- or nucleotide-excision repair and are difficult to interpret in terms of hazard for man. Further studies with additional genotoxicity assays would be required to make such a prediction. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****TIDSSKRIFT FOR DEN NORSKE LAEGEFORENING***** Bruseth S Enge A [Mistletoe in the treatment of cancer (see comments)] Misteltein i behandling av kreft. In: Tidsskr Nor Laegeforen (1993 Mar 30) 113(9):1058-60 ISSN: 0029-2001 (Published in Norwegian) Mistletoe (Viscum album) was introduced in the treatment of cancer in 1917. Today, extracts from the plant are used in adjuvant cancer therapy mainly as injections. The most important active agents are lectins, which have cytotoxic and immunostimulating effects. Mistletoe extracts have low toxicity. No fatal side effects have been reported. More than 40 clinical studies have been carried out, mainly at the Lukas Klinik in Switzerland and the Ludvig Boltzmann-Institute in Austria. Most of these studies claim that mistletoe has a positive effect, but were of poor methodological design. Therefore, in the light of our own positive experiences, we recommend a randomized multicentre study to evaluate the effect of mistletoe in cancer treatment. Comment in: Tidsskr Nor Laegeforen 1993 Aug 10;113(18):2284-5 €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****TROPICAL MEDICINE AND PARASITOLOGY***** Maraghi S Molyneux DH Wallbanks KR Differentiation of rodent trypanosomes of the subgenus Herpetosoma by lectins. In: Trop Med Parasitol (1989 Sep) 40(3):273-8 ISSN: 0177-2392 Trypomastigote forms of Trypanosoma microti, T. evotomys, T. grosi, T. musculi, and T. lewisi and trypomastigote and epimastigote forms of T. acomys were differentiated using 34 lectins and the Aminoff test for N-acetylneuraminic acid (NANA). Twelve of the lectins failed to agglutinate any of the above species. The number of lectins which agglutinated each species differed; T. mciroti, T. evotomys, T. grosi, T. musculi, T. lewisi and T. acomys (trypomastigote and epimastigote forms) were agglutinated by 7, 14, 7, 13, 11 and (11 and 10) lectins respectively. Some of the lectins were common in agglutinating all species of parasites, for example Bauhinia purpurea, Caragana aborescens and Viscum album. The minimum concentration of lectins which agglutinated each parasite was quite different. The agglutinations were cell body-cell body, flagellum- flagellum or flagellum-cell body. Most of the agglutinations were inhibited by their specific carbohydrates. The lowest concentrations of NANA was observed in T. lewisi (0.3 micrograms/ml) and the highest in T. musculi (4.5 micrograms/ml). The concentrations of NANA in T. microti, T. grosi and in T. acomys (trypomastigote and epimastigote forms) were 2, 1.8, 2.9, and (1.4 and 1.2) micrograms/ml respectively. Registry Numbers: 131-48-6 (N-Acetylneuraminic Acid) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****TUMORI***** Kuttan G Kuttan R Reduction of leukopenia in mice by "viscum album" administration during radiation and chemotherapy. In: Tumori (1993 Feb 28) 79(1):74-6 ISSN: 0300-8916 "Viscum album" extract, iscador, was found to reduce the leukocytopenia produced by radiation and cyclophosphamide treatment in animals. Weight loss due to radiation was considerably reduced by "Viscum album" extract whereas weight loss due to cyclophosphamide was not altered. Hemoglobin levels also were not affected by "Viscum album" extract administration. The results indicated that treatment with "Viscum album" extract reduces lymphocytopenia and hence could be used along with chemotherapy and radiation therapy. Registry Numbers: 50-18-0 (Cyclophosphamide) 53986-31-5 (iscador) 9034-51-9 (Hemoglobin A) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****YAO HSUEH HSUEH PAO [ACTA PHARMACEUTICA SINICA]***** Kong DY Li HT Luo SQ [Studies on the chemical components of Viscum coloratum VII. isolation and structure of viscumneoside VII] In: Yao Hsueh Hsueh Pao (1990) 25(8):608-11 ISSN: 0513-4870 (Published in Chinese) From the ethanol extract of Viscum coloratum (Kom.) Nakai, a new flavonoid has been isolated. Based on chemical and spectroscopic analysis, the structure of VII has been elucidated as rhamnazin-3-0- beta-D-apisoyl-(1----2)-[6"-O-(3-hydroxy-3- methylglutarate)]- glucoside and named Viscumneoside VII. Registry Numbers: 131749-61-6 (viscumneoside VII) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Kong DY 5th Li HT Luo SQ Lei XH [Studies on the chemical components of Viscum coloratum. VI. Chirality of the acyl group of viscumneoside IV] In: Yao Hsueh Hsueh Pao (1990) 25(5):349-52 ISSN: 0513-4870 (Published in Chinese) In order to determine the absolute configuration of the chiral center of viscumneoside IV, which was isolated from Viscum coloratum (Kom) Nakai, (R, S)-mevalonolactone was synthesized as shown in scheme 1. Then treatment with (S) (-)-1-phenylethylamine in THF gave two diasteromeric amides, which were transformed into the monoacetates and separated by HPLC. The first eluted peak (tR10.07 min.) had the (R)-configuration and the second one the (S)-configuration (tR11.20 min). Viscumneoside IV was treated with borane and hydrolyzed to give mevalonolactone which was treated with (S)-(-)-1-phenylethylamine in THF as mentioned above. The monoacetates of the resulting amides were subjected to HPLC. By comparison with the reference peaks, the absolute configuration at the acyl moiety of viscumneoside IV was shown to have the (R)-configuration. Registry Numbers: 119725-29-0 (viscumneoside IV) 150-97-0 (Mevalonic Acid) 503-48-0 (mevalonolactone) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Kong DY Li HT Luo SQ [Studies on the chemical components of Viscum coloratum. VIII. Isolation and structure of 3-beta-D-glucopyranosyloxy-butanol-2] In: Yao Hsueh Hsueh Pao (1992) 27(10):792-5 ISSN: 0513-4870 (Published in Chinese) From the ethanol extract of Viscum coloratum (Kom.) Nakai, a glucoside of aliphatic diol and three other glucosides were isolated. Based on chemical and spectroscopic analysis, the structures have been elucidated as 2-beta-D-glucosyl-3-methylpropanol (VIII), syringin (IX), eleatheroside E (X) and syringenin-4'-O-D- apiosylglucoside (XI). VIII is a new glucoside of aliphatic diol and named 3-beta-D-glucopyranosyloxy-butanol-2. Three other compounds (IX- XI) were found for the first time in this plant. Registry Numbers: 146763-54-4 (3-glucopyranosyloxy-butanol-2) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****ZEITSCHRIFT FUR NATURFORSCHUNG. SECTION C. JOURNAL OF BIOSCIENCES***** Saenz MT Ahumada MC Garcia MD Extracts from Viscum and Crataegus are cytotoxic against larynx cancer cells. In: Z Naturforsch [C] (1997 Jan-Feb) 52(1-2):42-4 ISSN: 0341-0382 The effects of hexanoic extracts of Viscum cruciatum Sieber parasitic on Crataegus monogyna Jacq. (I), Crataegus monogyna Jacq. parasitized with Viscum cruciatum Sieber (II), and Crataegus monogyna Jacq. non- parasitized (III), and of a triterpenes enriched fractions isolated from I, II and III (CFI, CFII, CFIII respectively), on the growth of HEp-2 cells have been evaluated. All the samples demonstrated significant cytotoxic activity against cultured HEp-2 cells, and all of them showed a stronger in vitro activity than 6-mercaptopurine solution used as a positive control. With the hexanoic extracts I, II and III almost similar activity was obtained, but the hexanoic extract I showed comparably better results. Almost complete inhibition was observed with triterpenes-enriched fractions CFI, CFII and CFIII, at the dose 6 micrograms/ml, after 72 h of treatment. The most intense response was obtained with the triterpenes-enriched fraction CFIII (from Crataegus monogyna non-parasitized), where the inhibition was 93%, but the fraction CFI and CFII showed similar inhibition (92% and 83%). €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€